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Entry
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- *602136 - PEROXISOME BIOGENESIS FACTOR 1; PEX1
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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">*602136</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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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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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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/602136">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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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000127980;t=ENST00000248633" 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=5189" 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=602136" 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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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000127980;t=ENST00000248633" 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_000466,NM_001282677,NM_001282678,XM_047420472,XM_047420473" 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_000466" 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=602136" 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=03682&isoform_id=03682_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/PEX1" 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/1669371,2655141,2827156,4505725,6015438,8134613,14289171,14289173,14289175,14289177,14289179,23242696,51094904,51094906,62088290,119597246,119597247,119597248,119597249,119597250,158259371,194374563,194375804,194380772,544186102,544186104,2217367413,2217367415,2462614767,2462614769" 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/O43933" 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=5189" 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=ENSG00000127980;t=ENST00000248633" 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=PEX1" 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=PEX1" 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+5189" 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/PEX1" 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:5189" 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/5189" 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=chr7&hgg_gene=ENST00000248633.9&hgg_start=92487025&hgg_end=92528520&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:8850" 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:8850" 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/pex1" 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=602136[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=602136[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000127980" 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=PEX1" 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=PEX1" 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=PEX1" 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.dbpex.org/" 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=PEX1&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/PA33192" 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:8850" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0013563.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1918632" 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/PEX1#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:1918632" 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/5189/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=5189" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00004191;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-070530-1" 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="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</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="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:602136" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</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://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5189" 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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<div><a href="https://reactome.org/content/query?q=PEX1&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> 238062008<br />
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<strong>ICD10CM:</strong> G60.1<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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602136
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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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PEROXISOME BIOGENESIS FACTOR 1; PEX1
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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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PEROXIN 1
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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=PEX1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PEX1</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>
|
|
Cytogenetic location: <a href="/geneMap/7/410?start=-3&limit=10&highlight=410">7q21.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:92487025-92528520&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'})">7:92,487,025-92,528,520</a> </span>
|
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</em>
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</strong>
|
|
<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;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<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>
|
|
Location
|
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</th>
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<th>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=234580,214100,601539" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
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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>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/410?start=-3&limit=10&highlight=410">
|
|
7q21.2
|
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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">
|
|
Heimler syndrome 1
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/234580"> 234580 </a>
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</span>
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<p><a href="#13" class="mim-tip-reference" title="Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., Valle, D., Gould, S. J. <strong>Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.</strong> Nature Genet. 17: 445-448, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398847</a>] [<a href="https://doi.org/10.1038/ng1297-445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398847">Reuber et al. (1997)</a> and <a href="#10" class="mim-tip-reference" title="Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., Dodt, G. <strong>Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.</strong> Nature Genet. 17: 449-452, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398848</a>] [<a href="https://doi.org/10.1038/ng1297-449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398848">Portsteffen et al. (1997)</a> identified the human ortholog of yeast PEX1, a gene required for peroxisomal matrix protein import. The gene encodes a 147-kD member of the AAA protein family (ATPases associated with diverse cellular activities). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9398848+9398847" 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 functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged 'enhanced' green fluorescent protein, <a href="#16" class="mim-tip-reference" title="Tamura, S., Okumoto, K., Toyama, R., Shimozawa, N., Tsukamoto, T., Suzuki, Y., Osumi, T., Kondo, N., Fujiki, Y. <strong>Human PEX1 cloned by functional complementation in a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.</strong> Proc. Nat. Acad. Sci. 95: 4350-4355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9539740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9539740</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9539740[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.8.4350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9539740">Tamura et al. (1998)</a> isolated a human PEX1 cDNA. This cDNA encoded a hydrophilic protein comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with human PEX1 was morphologically and biochemically restored for peroxisome biogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9539740" 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="#10" class="mim-tip-reference" title="Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., Dodt, G. <strong>Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.</strong> Nature Genet. 17: 449-452, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398848</a>] [<a href="https://doi.org/10.1038/ng1297-449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398848">Portsteffen et al. (1997)</a> detected 24 exons in the human PEX1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398848" 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 computer-based 'homology probing' using the yeast sequence to screen a database of expressed sequence tags (dbEST) for human cDNA clones, <a href="#10" class="mim-tip-reference" title="Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., Dodt, G. <strong>Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.</strong> Nature Genet. 17: 449-452, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398848</a>] [<a href="https://doi.org/10.1038/ng1297-449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398848">Portsteffen et al. (1997)</a> found a contig sequence localized to 7q21-q22 that exactly matched their cDNA. They identified the human PEX1 homolog and characterized its exon/intron structure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398848" 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><strong><em>Peroxisome Biogenesis Disorders 1A and 1B</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., Valle, D., Gould, S. J. <strong>Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.</strong> Nature Genet. 17: 445-448, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398847</a>] [<a href="https://doi.org/10.1038/ng1297-445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398847">Reuber et al. (1997)</a> found that expression of human PEX1 restored peroxisomal protein import in fibroblasts from 30 patients with peroxisomal biogenesis disorders of complementation group 1 (CG1; see PBD1A, <a href="/entry/214100">214100</a>). Additionally, they detected PEX1 mutations in multiple CG1 probands. A common PEX1 allele, gly843-to-asp (G843D; <a href="#0001">602136.0001</a>), was present in approximately half of the CG1 patients and was shown to have a deleterious effect on PEX1 activity. Phenotypic analysis of PEX1-deficient cells revealed severe defects in peroxisomal matrix protein import and destabilization of PEX5 (<a href="/entry/600414">600414</a>), the receptor for the type 1 peroxisomal targeting signal, even though peroxisomes were present in these cells and capable of importing peroxisomal membrane proteins. These data demonstrated an important role for PEX1 in peroxisome biogenesis and suggested that mutations in PEX1 are the most common cause of the peroxisomal biogenesis disorders (see <a href="/entry/601539">601539</a>). Homozygosity for the G843D mutation was found in patients with peroxisome biogenesis disorder-1B (PBD1B; <a href="/entry/601539">601539</a>), including at least 1 individual exhibiting neonatal adrenoleukodystrophy (NALD) as well as several cases of infantile Refsum disease (IRD). Heterozygosity for the G843D mutation (with other alleles not characterized) was found in cases of NALD, IRD, and Zellweger syndrome (ZS; <a href="/entry/214100">214100</a>) (<a href="#13" class="mim-tip-reference" title="Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., Valle, D., Gould, S. J. <strong>Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.</strong> Nature Genet. 17: 445-448, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398847</a>] [<a href="https://doi.org/10.1038/ng1297-445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398847">Reuber et al., 1997</a>). These 3 disorders appeared to represent a continuum of clinical features that are most severe in ZS, milder in NALD, and least severe in IRD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398847" 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="#10" class="mim-tip-reference" title="Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., Dodt, G. <strong>Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.</strong> Nature Genet. 17: 449-452, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398848</a>] [<a href="https://doi.org/10.1038/ng1297-449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398848">Portsteffen et al. (1997)</a> identified 3 mutant alleles in CG1 patients, including the G843D mutation, which was found in homozygosity in 1 patient and heterozygosity in another. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Tamura, S., Okumoto, K., Toyama, R., Shimozawa, N., Tsukamoto, T., Suzuki, Y., Osumi, T., Kondo, N., Fujiki, Y. <strong>Human PEX1 cloned by functional complementation in a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.</strong> Proc. Nat. Acad. Sci. 95: 4350-4355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9539740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9539740</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9539740[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.8.4350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9539740">Tamura et al. (1998)</a> demonstrated that human PEX1 expression restored peroxisomal protein import in fibroblasts from 3 patients with Zellweger syndrome and neonatal adrenoleukodystrophy of complementation group 1, which is the peroxisome biogenesis disorder (PBD) of highest incidence. <a href="#16" class="mim-tip-reference" title="Tamura, S., Okumoto, K., Toyama, R., Shimozawa, N., Tsukamoto, T., Suzuki, Y., Osumi, T., Kondo, N., Fujiki, Y. <strong>Human PEX1 cloned by functional complementation in a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.</strong> Proc. Nat. Acad. Sci. 95: 4350-4355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9539740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9539740</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9539740[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.8.4350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9539740">Tamura et al. (1998)</a> found that a patient with Zellweger syndrome was compound heterozygous for inactivating mutations of the PEX1 gene (<a href="#0002">602136.0002</a>, <a href="#0003">602136.0003</a>). The cDNAs corresponding to these PEX1 mutations were defective in peroxisome-restoring activity when expressed in the patient's fibroblasts as well as in ZP107 cells. This method of identifying PEX1 cDNA complements that used by <a href="#13" class="mim-tip-reference" title="Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., Valle, D., Gould, S. J. <strong>Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.</strong> Nature Genet. 17: 445-448, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398847</a>] [<a href="https://doi.org/10.1038/ng1297-445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398847">Reuber et al. (1997)</a> and <a href="#10" class="mim-tip-reference" title="Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., Dodt, G. <strong>Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.</strong> Nature Genet. 17: 449-452, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398848</a>] [<a href="https://doi.org/10.1038/ng1297-449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398848">Portsteffen et al. (1997)</a>, who isolated the human PEX1 gene by a homology search of a human EST database using a yeast PEX1 sequence. All 3 studies demonstrated unequivocally that PEX1 is the causative gene for complementation group 1 peroxisomal disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9539740+9398848+9398847" 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 fibroblasts from all CG1 infantile Refsum disease (IRD) patients examined, <a href="#6" class="mim-tip-reference" title="Imamura, A., Tamura, S., Shimozawa, N., Suzuki, Y., Zhang, Z., Tsukamoto, T., Orii, T., Kondo, N., Osumi, T., Fujiki, Y. <strong>Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders.</strong> Hum. Molec. Genet. 7: 2089-2094, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817926</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817926">Imamura et al. (1998)</a> found that peroxisomes were morphologically and biochemically formed at 30 degrees centigrade but not at 37 degrees centigrade; on the other hand, almost no peroxisomes were seen in Zellweger syndrome and neonatal adrenoleukodystrophy cells, even at 30 degrees centigrade. The mutation G843D (<a href="#0001">602136.0001</a>) was found in the PEX1 allele of most CG1 IRD patients. The mutant PEX1 G843D gave rise to the same temperature-sensitive phenotype on CG1 CHO cell mutants upon transfection. Collectively, these results demonstrated temperature-sensitive peroxisome assembly to be responsible for the mildness of the clinical features of PEX1-defective IRD of complementation group 1. <a href="#6" class="mim-tip-reference" title="Imamura, A., Tamura, S., Shimozawa, N., Suzuki, Y., Zhang, Z., Tsukamoto, T., Orii, T., Kondo, N., Osumi, T., Fujiki, Y. <strong>Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders.</strong> Hum. Molec. Genet. 7: 2089-2094, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817926</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817926">Imamura et al. (1998)</a> suggested that the severity of peroxisome biogenesis disorder can be prognosticated by examining the temperature-sensitive complementation of peroxisomes in patient fibroblasts. This prognostic tool may encourage pediatricians to treat the milder PBD variants with therapies such as an oral administration of docosahexaenoic acid. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Collins, C. S., Gould, S. J. <strong>Identification of a common PEX1 mutation in Zellweger syndrome.</strong> Hum. Mutat. 14: 45-53, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447258</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10447258">Collins and Gould (1999)</a> analyzed all 24 exons of the PEX1 gene in 4 patients with CG1 Zellweger syndrome, including 2 patients in whom <a href="#3" class="mim-tip-reference" title="Gartner, J., Moser, H., Valle, D. <strong>Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome.</strong> Nature Genet. 1: 16-23, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301993</a>] [<a href="https://doi.org/10.1038/ng0492-16" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301993">Gartner et al. (1992)</a> had found variants in the PMP70 gene (<a href="/entry/170995#0001">170995.0001</a>, <a href="/entry/170995#0002">170995.0002</a>). PEX1 mutations were detected in all 4 patients, including a 1-bp insertion (2097insT; <a href="#0004">602136.0004</a>) in exon 13 that was present in 3 of the 4 patients. Screening for the 2097insT mutation in 32 additional CG1 patients revealed 3 who were homozygous and 12 who were heterozygous for the insertion. <a href="#1" class="mim-tip-reference" title="Collins, C. S., Gould, S. J. <strong>Identification of a common PEX1 mutation in Zellweger syndrome.</strong> Hum. Mutat. 14: 45-53, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447258</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10447258">Collins and Gould (1999)</a> noted that in contrast to the other common PEX1 mutation, G843D, which is associated with a trend toward the mild end of the ZS phenotypic spectrum, this second common PEX1 mutation is associated with severe phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1301993+10447258" 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>Mutations in PEX1 account for approximately 65% of patients with PBDs. <a href="#17" class="mim-tip-reference" title="Walter, C., Gootjes, J., Mooijer, P. A., Portsteffen, H., Klein, C., Waterham, H. R., Barth, P. G., Epplen, J. T., Kunau, W.-H., Wanders, R. J. A., Dodt, G. <strong>Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels.</strong> Am. J. Hum. Genet. 69: 35-48, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389485[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389485">Walter et al. (2001)</a> found that complete lack of PEX1 protein is associated with severe Zellweger syndrome; however, residual amounts of PEX1 protein were found in patients with the milder phenotypes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD). Most of the IRD patients carried at least 1 copy of the common G843D allele. When patient fibroblasts harboring this allele were grown at 30 degrees centigrade, a 2- to 3-fold increase in PEX1 protein levels was observed, associated with the recovery of peroxisomal function. This suggested that the G843D missense mutation results in a misfolded protein, which is more stable at lower temperatures. <a href="#17" class="mim-tip-reference" title="Walter, C., Gootjes, J., Mooijer, P. A., Portsteffen, H., Klein, C., Waterham, H. R., Barth, P. G., Epplen, J. T., Kunau, W.-H., Wanders, R. J. A., Dodt, G. <strong>Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels.</strong> Am. J. Hum. Genet. 69: 35-48, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389485</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389485[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/321265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389485">Walter et al. (2001)</a> concluded that their search for the factors and/or mechanisms that determine the stability of mutant PEX1 proteins can be a first step in the development of therapeutic strategies for patients with mild PBDs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the subgroup of PBD patients with ZS, NALD, and IRD, more than half have mutations in the PEX1 gene. <a href="#8" class="mim-tip-reference" title="Maxwell, M. A., Allen, T., Solly, P. B., Svingen, T., Paton, B. C., Crane, D. I. <strong>Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients.</strong> Hum. Mutat. 20: 342-351, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12402331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12402331</a>] [<a href="https://doi.org/10.1002/humu.10128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12402331">Maxwell et al. (2002)</a> identified 5 novel mutations in an Australasian cohort of PEX1-deficient PBD patients, including a frameshift mutation in exon 18 (<a href="#0005">602136.0005</a>) that was present in moderately high frequency (approximately 10% of alleles). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12402331" 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="Majewski, J., Wang, Z., Lopez, I., Al Humaid, S., Ren, H., Racine, J., Bazinet, A., Mitchel, G., Braverman, N., Koenekoop, R. K. <strong>A new ocular phenotype associated with an unexpected but known systemic disorder and mutation: novel use of genomic diagnostics and exome sequencing.</strong> J. Med. Genet. 48: 593-596, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21862673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21862673</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21862673">Majewski et al. (2011)</a> identified biallelic mutations in the PEX1 gene in 2 patients. Patient 1 was a 28-year-old woman with PBD1B who had normal cognition and a history of Leber congenital amaurosis (LCA; see <a href="/entry/204000">204000</a>). She was homozygous for the common G843D mutation (<a href="#0001">602136.0001</a>). Patient 2 was an infant with PBD1A who presented with LCA at 9 months of age and had developmental delay, hypotonia, and seizures at 20 months of age. She was compound heterozygous for the G843D mutation and a 1-bp insertion (c.2098insT; <a href="#0010">602136.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21862673" 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>Heimler Syndrome 1</em></strong></p><p>
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In affected individuals from 4 unrelated families with sensorineural hearing loss, enamel hypoplasia, and nail defects (HMLR1; <a href="/entry/234580">234580</a>), <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a> identified biallelic mutations in the PEX1 gene (<a href="#0004">602136.0004</a> and <a href="#0006">602136.0006</a>-<a href="#0009">602136.0009</a>). The authors noted that in contrast to patients with PBDs at the severe end of the clinical spectrum, these patients showed no identifiable dysmorphic or additional neurologic features. Complementation assays in PEX1-null cells transfected with variants from patients with Heimler syndrome-1 demonstrated that all affected individuals had at least 1 PEX variant with residual activity in peroxisomal biogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26387595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Maxwell, M. A., Allen, T., Solly, P. B., Svingen, T., Paton, B. C., Crane, D. I. <strong>Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients.</strong> Hum. Mutat. 20: 342-351, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12402331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12402331</a>] [<a href="https://doi.org/10.1002/humu.10128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12402331">Maxwell et al. (2002)</a> found a close correlation between cellular phenotype, disease severity, and PEX1 genotype in an Australasian cohort of PEX1-deficient PBD patients. <a href="#11" class="mim-tip-reference" title="Preuss, N., Brosius, U., Biermanns, M., Muntau, A. C., Conzelmann, E., Gartner, J. <strong>PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease.</strong> Pediat. Res. 51: 706-714, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12032265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12032265</a>] [<a href="https://doi.org/10.1203/00006450-200206000-00008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12032265">Preuss et al. (2002)</a> also found a close correlation between PEX1 genotype and age of survival in 16 well-documented Zellweger spectrum patients, which supported the usefulness of determining the exact PEX1 mutations in patients. Missense mutations caused milder disease, while insertions, deletions, and nonsense mutations were associated with severe clinical disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12032265+12402331" 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 21 of 31 patients with PBDs, <a href="#9" class="mim-tip-reference" title="Poll-The, B. T., Gootjes, J., Duran, M., de Klerk, J. B. C., Maillette de Buy Wenniger-Prick, L. J., Admiraal, R. J. C., Waterham, H. R., Wanders, R. J. A., Barth, P. G. <strong>Peroxisome biogenesis disorders with prolonged survival: phenotypic expression in a cohort of 31 patients.</strong> Am. J. Med. Genet. 126A: 333-338, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15098231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15098231</a>] [<a href="https://doi.org/10.1002/ajmg.a.20664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15098231">Poll-The et al. (2004)</a> identified mutations in the PEX1 gene. The most common mutations were G843D (<a href="#0001">602136.0001</a>) and 2097insT (<a href="#0004">602136.0004</a>), which were associated with mild and severe Zellweger syndrome, respectively. Patients homozygous for G843D tended to have a better developmental outcome than did patients compound heterozygous for the 2 mutations. However, there were exceptions, suggesting that unknown factors influence the ultimate phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15098231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 168 Zellweger spectrum patients, including 33 of their own, <a href="#14" class="mim-tip-reference" title="Rosewich, H., Ohlenbusch, A., Gartner, J. <strong>Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations.</strong> J. Med. Genet. 42: e58, 2005. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16141001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16141001</a>] [<a href="https://doi.org/10.1136/jmg.2005.033324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16141001">Rosewich et al. (2005)</a> found that the G843D and 2097insT mutations accounted for over 80% of all abnormal PEX1 alleles. Most of the mutations were distributed over the 2 AAA cassettes with the 2 functional protein domains, D1 and D2, and the highly conserved Walker motifs. PEX1 mutations could be divided into 2 classes: class I mutations led to residual PEX1 protein levels and function and a milder phenotype; class II mutations almost abolished PEX1 protein levels and function, resulting in a severe phenotype. Patients who were compound heterozygous for a class I and a class II mutation had an intermediate phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16141001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Crane, D. I., Maxwell, M. A., Paton, B. C. <strong>PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders.</strong> Hum. Mutat. 26: 167-175, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16086329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16086329</a>] [<a href="https://doi.org/10.1002/humu.20211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16086329">Crane et al. (2005)</a> provided a detailed review of the mutations identified in the PEX1 gene. Mutations that produce premature termination codons are distributed throughout the PEX1 gene, whereas the majority of missense mutations segregate with the 2 essential AAA domains of the PEX1 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16086329" 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=602136[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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<strong>.0001 PEROXISOME BIOGENESIS DISORDER 1B</strong>
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PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER), INCLUDED
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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> rs61750420 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750420;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/rs61750420?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=rs61750420" 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=rs61750420" 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=RCV000007946 OR RCV000022416 OR RCV000032927 OR RCV000078922 OR RCV000345695 OR RCV000661947 OR RCV000763596 OR RCV000791271 OR RCV001004322 OR RCV001074120 OR RCV001266794 OR RCV001376560 OR RCV001731280 OR RCV003398462 OR RCV004786245" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007946, RCV000022416, RCV000032927, RCV000078922, RCV000345695, RCV000661947, RCV000763596, RCV000791271, RCV001004322, RCV001074120, RCV001266794, RCV001376560, RCV001731280, RCV003398462, RCV004786245" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007946...</a>
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<p>In patients with peroxisome biogenesis disorder-1B (PBD1B; <a href="/entry/601539">601539</a>), including at least 1 individual exhibiting neonatal adrenoleukodystrophy (NALD) as well as several cases of infantile Refsum disease (IRD), <a href="#13" class="mim-tip-reference" title="Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., Valle, D., Gould, S. J. <strong>Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.</strong> Nature Genet. 17: 445-448, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398847</a>] [<a href="https://doi.org/10.1038/ng1297-445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398847">Reuber et al. (1997)</a> identified homozygosity for a gly843-to-asp (G843D) substitution in the PEX1 gene. In addition, the mutation was found in heterozygous state in cases of NALD, IRD, and Zellweger syndrome (PBD1A; <a href="/entry/214100">214100</a>), with the other alleles uncharacterized. Functional analysis in patient fibroblasts suggested that the G843D mutant was only about 15% as active as wildtype PEX1. <a href="#10" class="mim-tip-reference" title="Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., Dodt, G. <strong>Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.</strong> Nature Genet. 17: 449-452, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398848</a>] [<a href="https://doi.org/10.1038/ng1297-449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398848">Portsteffen et al. (1997)</a> also identified this mutation in homozygous and heterozygous state in patients with peroxisome biogenesis disorders of complementation group 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9398848+9398847" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 23 German patients with peroxisomal biogenesis disorder of complementation group 1, <a href="#4" class="mim-tip-reference" title="Gartner, J., Preuss, N., Brosius, U., Biermanns, M. <strong>Mutations in PEX1 in peroxisome biogenesis disorders: G843D and a mild clinical phenotype.</strong> J. Inherit. Metab. Dis. 22: 311-313, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10384394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10384394</a>] [<a href="https://doi.org/10.1023/a:1005599903632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10384394">Gartner et al. (1999)</a> found that 8 were either homozygous or heterozygous for a c.2528G-A transition in exon 15 of PEX1, producing a G843D amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10384394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 28-year-old woman (patient 1) with PBD1B, <a href="#7" class="mim-tip-reference" title="Majewski, J., Wang, Z., Lopez, I., Al Humaid, S., Ren, H., Racine, J., Bazinet, A., Mitchel, G., Braverman, N., Koenekoop, R. K. <strong>A new ocular phenotype associated with an unexpected but known systemic disorder and mutation: novel use of genomic diagnostics and exome sequencing.</strong> J. Med. Genet. 48: 593-596, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21862673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21862673</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21862673">Majewski et al. (2011)</a> identified homozygosity for the G843D mutation in the PEX1 gene. The mutation, which was identified by next-generation sequencing and confirmed by Sanger sequencing, was present in the carrier state in the parents. The patient had normal cognition and a history of Leber congenital amaurosis (LCA; see <a href="/entry/204000">204000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21862673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient (patient 2) with PBD1A, <a href="#7" class="mim-tip-reference" title="Majewski, J., Wang, Z., Lopez, I., Al Humaid, S., Ren, H., Racine, J., Bazinet, A., Mitchel, G., Braverman, N., Koenekoop, R. K. <strong>A new ocular phenotype associated with an unexpected but known systemic disorder and mutation: novel use of genomic diagnostics and exome sequencing.</strong> J. Med. Genet. 48: 593-596, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21862673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21862673</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21862673">Majewski et al. (2011)</a> identified compound heterozygous mutations in the PEX1 gene: G843D and a 1-bp insertion (c.2098insT; <a href="#0010">602136.0010</a>), resulting in a frameshift and premature termination (Ile700TyrfsTer42). The G843D mutation was identified by restriction enzyme analysis in a cohort of patients with LCA, and the c.2098insT mutation was identified by Sanger sequencing of the PEX1 gene. The patient presented with LCA at 9 months of age and had developmental delay, hypotonia, and seizures at 20 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21862673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Waterham, H. R., Ebberink, M. S. <strong>Genetics and molecular basis of human peroxisome biogenesis disorders.</strong> Biochim. Biophys. Acta 1822: 1430-1441, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22871920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22871920</a>] [<a href="https://doi.org/10.1016/j.bbadis.2012.04.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22871920">Waterham and Ebberink (2012)</a> noted that the G843D mutation reduces the binding between PEX1 and PEX6 (<a href="/entry/601498">601498</a>). The effect of the mutation is relatively mild, and cells of patients with this mutation often display peroxisomal mosaicism when cultured at 37 degrees Celsius. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22871920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Waterham, H. R., Ebberink, M. S. <strong>Genetics and molecular basis of human peroxisome biogenesis disorders.</strong> Biochim. Biophys. Acta 1822: 1430-1441, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22871920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22871920</a>] [<a href="https://doi.org/10.1016/j.bbadis.2012.04.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22871920">Waterham and Ebberink (2012)</a> noted that mutations in the PEX1 gene have a frequency of 58.9% among patients with Zellweger spectrum disorders. <a href="#15" class="mim-tip-reference" title="Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., Moser, H. W. <strong>Peroxisome biogenesis disorders.</strong> Biochim. Biophys. Acta 1763: 1733-1748, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17055079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17055079</a>] [<a href="https://doi.org/10.1016/j.bbamcr.2006.09.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17055079">Steinberg et al. (2006)</a> gave the allele frequency of the G843D mutation as 0.43, making it the most common mutation in PEX1-deficient patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17055079+22871920" 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">rs121434455 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434455;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=rs121434455" 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=rs121434455" 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=RCV000007949 OR RCV000763597 OR RCV001248383 OR RCV003473054 OR RCV003480024" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007949, RCV000763597, RCV001248383, RCV003473054, RCV003480024" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007949...</a>
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<p>In a patient with Zellweger syndrome of complementation group 1 (PBD1A; <a href="/entry/214100">214100</a>), <a href="#16" class="mim-tip-reference" title="Tamura, S., Okumoto, K., Toyama, R., Shimozawa, N., Tsukamoto, T., Suzuki, Y., Osumi, T., Kondo, N., Fujiki, Y. <strong>Human PEX1 cloned by functional complementation in a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.</strong> Proc. Nat. Acad. Sci. 95: 4350-4355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9539740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9539740</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9539740[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.8.4350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9539740">Tamura et al. (1998)</a> identified compound heterozygosity for a 1191T-C mutation in the PEX1 gene, resulting in an leu664-to-pro (L664P) substitution, and a 171-bp deletion of nucleotide residues 1,900 to 2,070 (<a href="#0003">602136.0003</a>). Northern blot analysis of patient and control mRNA revealed a 4.3-kb band in both, suggesting that PEX1 transcription was unaffected in the patient. Functional analysis demonstrated that cDNAs corresponding to both PEX1 mutations were defective in peroxisome-restoring activity when expressed in the patient's fibroblasts as well as in ZP107 cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9539740" 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>For discussion of the 171-bp deletion of nucleotide residues 1,900 to 2,070 in the PEX1 gene that was found in compound heterozygous state in a patient with Zellweger syndrome of complementation group A (PBD1A; <a href="/entry/214100">214100</a>) by <a href="#16" class="mim-tip-reference" title="Tamura, S., Okumoto, K., Toyama, R., Shimozawa, N., Tsukamoto, T., Suzuki, Y., Osumi, T., Kondo, N., Fujiki, Y. <strong>Human PEX1 cloned by functional complementation in a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.</strong> Proc. Nat. Acad. Sci. 95: 4350-4355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9539740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9539740</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9539740[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.8.4350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9539740">Tamura et al. (1998)</a>, see <a href="#0002">602136.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9539740" 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>.0004 PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER)</strong>
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HEIMLER SYNDROME 1, INCLUDED
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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> rs61750415 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750415;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/rs61750415?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=rs61750415" 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=rs61750415" 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=RCV000007953 OR RCV000078918 OR RCV000201307 OR RCV000500705 OR RCV000850579 OR RCV000853332 OR RCV001004324 OR RCV001073754 OR RCV001376645 OR RCV002512885 OR RCV003415676 OR RCV004814857" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007953, RCV000078918, RCV000201307, RCV000500705, RCV000850579, RCV000853332, RCV001004324, RCV001073754, RCV001376645, RCV002512885, RCV003415676, RCV004814857" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007953...</a>
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<p>In 3 patients with Zellweger syndrome (PBD1A; <a href="/entry/214100">214100</a>), including a severely affected patient who was studied by <a href="#3" class="mim-tip-reference" title="Gartner, J., Moser, H., Valle, D. <strong>Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome.</strong> Nature Genet. 1: 16-23, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301993</a>] [<a href="https://doi.org/10.1038/ng0492-16" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301993">Gartner et al. (1992)</a> (patient PBD002) and another patient in whom <a href="#13" class="mim-tip-reference" title="Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., Valle, D., Gould, S. J. <strong>Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.</strong> Nature Genet. 17: 445-448, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398847</a>] [<a href="https://doi.org/10.1038/ng1297-445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398847">Reuber et al. (1997)</a> had identified a PEX1 splice donor mutation, <a href="#1" class="mim-tip-reference" title="Collins, C. S., Gould, S. J. <strong>Identification of a common PEX1 mutation in Zellweger syndrome.</strong> Hum. Mutat. 14: 45-53, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447258</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10447258">Collins and Gould (1999)</a> identified homozygosity or compound heterozygosity for a 1-bp insertion (c.2097insT) in exon 13 of the PEX1 gene. Screening for 2097insT in 32 additional CG1 patients revealed that 3 were homozygous and 12 heterozygous for the insertion. The authors concluded that 2097insT is a common allele in the CG1 patient population, and noted that in contrast to the other common mutation, G843D (<a href="#0001">602136.0001</a>), which is associated with a trend toward the mild end of the ZS phenotypic spectrum, this second common PEX1 mutation is associated with severe phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10447258+1301993+9398847" 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="#15" class="mim-tip-reference" title="Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., Moser, H. W. <strong>Peroxisome biogenesis disorders.</strong> Biochim. Biophys. Acta 1763: 1733-1748, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17055079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17055079</a>] [<a href="https://doi.org/10.1016/j.bbamcr.2006.09.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17055079">Steinberg et al. (2006)</a> gave the allele frequency of this mutation as 0.35 in PEX1-deficient patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17055079" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a brother and sister with Heimler syndrome-1 (HMLR1; <a href="/entry/234580">234580</a>), originally reported by <a href="#5" class="mim-tip-reference" title="Heimler, A., Fox, J. E., Hershey, J. E., Crespi, P. <strong>Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs.</strong> Am. J. Med. Genet. 39: 192-195, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063923</a>] [<a href="https://doi.org/10.1002/ajmg.1320390214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2063923">Heimler et al. (1991)</a>, <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a> identified compound heterozygosity for the c.2097dupT mutation (c.2097dupT, NM_000466.2) in the PEX1 gene and a c.2114T-G transversion, resulting in a leu705-to-trp (L705W; <a href="#0006">602136.0006</a>) substitution. In an unrelated 24-year-old woman with HMLR1, they identified compound heterozygosity for the 2097dupT mutation and a c.1742G-C transversion, resulting in an arg581-to-pro (R581P; <a href="#0007">602136.0007</a>) substitution. The mutations segregated with disease in both families, and were not found in 770 in-house exomes; in addition, the L705W mutation was not found in public databases, whereas the R581P mutation was present in 1 of 121,398 alleles in the ExAC Browser (minor allele frequency less than 0.000033). The 3 affected individuals all had sensorineural hearing loss, enamel hypoplasia, and nail defects, but did not exhibit dysmorphism or additional neurologic features. Complementation assays in transfected PEX1-null cells demonstrated that the c.2097dupT variant resulted in no complementation, whereas transfection with the c.1742G-C and c.2114T-G variants rescued peroxisomal biogenesis in 23% and 58% of cells, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26387595+2063923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER)</strong>
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PEROXISOME BIOGENESIS DISORDER 1B, INCLUDED
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PEX1, 1-BP DEL, 2916A
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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> rs61750426 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750426;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/rs61750426?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=rs61750426" 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=rs61750426" 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=RCV000169435 OR RCV000414630 OR RCV000588350 OR RCV001004318 OR RCV001201389 OR RCV002470783 OR RCV003474914 OR RCV005042357" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169435, RCV000414630, RCV000588350, RCV001004318, RCV001201389, RCV002470783, RCV003474914, RCV005042357" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169435...</a>
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<p>Among 72 mutant alleles from Australasian patients with Zellweger syndrome (ZS; <a href="/entry/214100">214100</a>), neonatal adrenoleukodystrophy (NALD; see <a href="/entry/601539">601539</a>), and infantile Refsum disease (see <a href="/entry/601539">601539</a>), <a href="#8" class="mim-tip-reference" title="Maxwell, M. A., Allen, T., Solly, P. B., Svingen, T., Paton, B. C., Crane, D. I. <strong>Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients.</strong> Hum. Mutat. 20: 342-351, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12402331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12402331</a>] [<a href="https://doi.org/10.1002/humu.10128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12402331">Maxwell et al. (2002)</a> found that 7 (9.7%) had a 1-bp deletion, 2916delA, in exon 18 of the PEX1 gene, causing a frameshift mutation after gly973 and resulting in nonsense-mediated mRNA decay. The mutation resulted in complete loss of PEX1 function and was associated with a severe Zellweger syndrome phenotype. This was the third most common mutation in this cohort after the G843D (<a href="#0001">602136.0001</a>) and exon 13 frameshift (<a href="#0004">602136.0004</a>) mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12402331" 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>.0006 HEIMLER SYNDROME 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs863225084 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863225084;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/rs863225084?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=rs863225084" 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=rs863225084" 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=RCV000201290 OR RCV001075286 OR RCV001810437 OR RCV002517304 OR RCV003417729 OR RCV004701263" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201290, RCV001075286, RCV001810437, RCV002517304, RCV003417729, RCV004701263" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201290...</a>
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<p>For discussion of the c.2114T-G transversion (c.2114T-G, NM_000466.2) in the PEX1 gene, resulting in a leu705-to-trp (L705W) substitution, that was found in compound heterozygous state in 2 sibs with Heimler syndrome-1 (HMLR1; <a href="/entry/234580">234580</a>) by <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a>, see <a href="#0004">602136.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26387595" 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> rs370483961 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs370483961;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/rs370483961?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=rs370483961" 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=rs370483961" 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=RCV000201302 OR RCV001075087 OR RCV001377625 OR RCV002500626" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201302, RCV001075087, RCV001377625, RCV002500626" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201302...</a>
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<p>For discussion of the c.1742G-C transversion (c.1742G-C, NM_000466.2) in the PEX1 gene, resulting in an arg581-to-pro (R581P) substitution, that was found in compound heterozygous state in 2 unrelated patients with Heimler syndrome-1 (HMLR1; <a href="/entry/234580">234580</a>) by <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a>, see <a href="#0004">602136.0004</a> and <a href="#0008">602136.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26387595" 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 HEIMLER SYNDROME 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs756876301 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs756876301;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/rs756876301?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=rs756876301" 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=rs756876301" 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=RCV000201308 OR RCV000633316 OR RCV001004518 OR RCV001376605 OR RCV001526999 OR RCV001795328 OR RCV003422106 OR RCV005031756" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201308, RCV000633316, RCV001004518, RCV001376605, RCV001526999, RCV001795328, RCV003422106, RCV005031756" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201308...</a>
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<p>In a 19-year-old Irish woman with sensorineural hearing loss, enamel hypoplasia, and nail defects (HMLR1; <a href="/entry/234580">234580</a>), <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a> identified compound heterozygosity for a splice site mutation (c.1239+1G-T, NM_000466.2) in intron 5 of the PEX1 gene, and a c.1742G-C transversion resulting in an arg581-to-pro (R581P; <a href="#0007">602136.0007</a>) substitution. <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a> noted that the intron 5 splice site mutation had been identified in compound heterozygosity with a PEX1 frameshift mutation in a patient with a peroxisome biogenesis disorder in the Zellweger syndrome spectrum (see PBD1A, <a href="/entry/214100">214100</a>) by <a href="#19" class="mim-tip-reference" title="Yik, W. Y., Steinberg, S. J., Moser, A. B., Moser, H. W., Hacia, J. G. <strong>Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.</strong> Hum. Mutat. 30: E467-E480, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19105186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19105186</a>] [<a href="https://doi.org/10.1002/humu.20932" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19105186">Yik et al. (2009)</a>. <a href="#19" class="mim-tip-reference" title="Yik, W. Y., Steinberg, S. J., Moser, A. B., Moser, H. W., Hacia, J. G. <strong>Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.</strong> Hum. Mutat. 30: E467-E480, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19105186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19105186</a>] [<a href="https://doi.org/10.1002/humu.20932" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19105186">Yik et al. (2009)</a> reported no clinical information for the patient with the Zellweger spectrum disorder, but <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a> stated that the Irish patient did not exhibit dysmorphism or additional neurologic features. The mutations segregated with disease in the family. The previously unreported c.1742G-C mutation was not found in 770 in-house exomes but was present in 1 of 121,398 alleles in the ExAC Browser (minor allele frequency less than 0.000033). Complementation assays in PEX1-null cells demonstrated that transfection with the c.1742G-C variant rescued peroxisomal biogenesis in 23% of cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26387595+19105186" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 HEIMLER SYNDROME 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs863225085 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863225085;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=rs863225085" 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=rs863225085" 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=RCV000201292" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201292" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201292</a>
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<p>In a Moroccan sister and brother with sensorineural hearing loss, enamel hypoplasia, and nail defects (HMLR1; <a href="/entry/234580">234580</a>), <a href="#12" class="mim-tip-reference" title="Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others. <strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong> Am. J. Hum. Genet. 97: 535-545, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26387595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26387595</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26387595[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26387595">Ratbi et al. (2015)</a> identified homozygosity for a c.3750G-A transition (c.3750G-A, NM_000466.2) in exon 23 of the PEX1 gene, resulting in a trp1250-to-ter (W1250X) substitution. The mutation segregated with disease in the family and was not found in 250 ethnically matched controls, 770 in-house exomes, or in public databases. Analysis of patient plasma, erythrocytes, and fibroblasts did not show any peroxisomal biochemical aberrations, consistent with their relatively very mild disease; however, immunofluorescence microscopy of patient fibroblasts revealed a mosaic peroxisomal pattern similar to that previously associated with hypomorphic variants. Complementation assays in PEX1-null cells demonstrated that transfection with the c.3750G-A variant rescued peroxisomal biogenesis in approximately 30% of cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26387595" 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=RCV000007953 OR RCV000078918 OR RCV000201307 OR RCV000500705 OR RCV000850579 OR RCV000853332 OR RCV001004324 OR RCV001073754 OR RCV001376645 OR RCV002512885 OR RCV003415676 OR RCV004814857" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007953, RCV000078918, RCV000201307, RCV000500705, RCV000850579, RCV000853332, RCV001004324, RCV001073754, RCV001376645, RCV002512885, RCV003415676, RCV004814857" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007953...</a>
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<p>For discussion of the 1-bp insertion (c.2098insT) in the PEX1 gene, resulting in a frameshift and premature termination (Ile700TyrfsTer42), that was found in compound heterozygous state in a patient with peroxisome biogenesis disorder-1A (PBD1A; <a href="/entry/214100">214100</a>) by <a href="#7" class="mim-tip-reference" title="Majewski, J., Wang, Z., Lopez, I., Al Humaid, S., Ren, H., Racine, J., Bazinet, A., Mitchel, G., Braverman, N., Koenekoop, R. K. <strong>A new ocular phenotype associated with an unexpected but known systemic disorder and mutation: novel use of genomic diagnostics and exome sequencing.</strong> J. Med. Genet. 48: 593-596, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21862673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21862673</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100288" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21862673">Majewski et al. (2011)</a>, see <a href="#0001">602136.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21862673" 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>REFERENCES</strong>
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Collins, C. S., Gould, S. J.
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<strong>Identification of a common PEX1 mutation in Zellweger syndrome.</strong>
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Hum. Mutat. 14: 45-53, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447258</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10447258" 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)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J" target="_blank">Full Text</a>]
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Crane, D. I., Maxwell, M. A., Paton, B. C.
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<strong>PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders.</strong>
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Hum. Mutat. 26: 167-175, 2005.
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[<a href="https://doi.org/10.1016/j.bbadis.2012.04.006" target="_blank">Full Text</a>]
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Yik, W. Y., Steinberg, S. J., Moser, A. B., Moser, H. W., Hacia, J. G.
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<strong>Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.</strong>
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Hum. Mutat. 30: E467-E480, 2009. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19105186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19105186</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19105186" 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.20932" 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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<span class="mim-text-font">
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Hilary J. Vernon - updated : 02/09/2023
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Marla J. F. O'Neill - updated : 10/27/2015<br>Cassandra L. Kniffin - updated : 1/3/2006<br>Victor A. McKusick - updated : 12/20/2005<br>Natalie E. Krasikov - updated : 8/10/2004<br>Victor A. McKusick - updated : 5/11/2004<br>Victor A. McKusick - updated : 11/21/2002<br>Victor A. McKusick - updated : 9/4/2001<br>Victor A. McKusick - updated : 7/15/1999<br>Victor A. McKusick - updated : 1/6/1999<br>Victor A. McKusick - updated : 5/21/1998
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Victor A. McKusick : 12/1/1997
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carol : 02/09/2023
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alopez : 11/03/2015<br>alopez : 10/27/2015<br>carol : 9/28/2015<br>mcolton : 8/18/2015<br>carol : 10/3/2013<br>alopez : 10/25/2012<br>alopez : 10/24/2012<br>alopez : 10/22/2010<br>carol : 4/18/2006<br>wwang : 1/9/2006<br>ckniffin : 1/3/2006<br>carol : 12/22/2005<br>terry : 12/20/2005<br>carol : 8/11/2004<br>terry : 8/10/2004<br>tkritzer : 7/20/2004<br>tkritzer : 6/9/2004<br>terry : 5/11/2004<br>joanna : 3/17/2004<br>tkritzer : 11/27/2002<br>tkritzer : 11/25/2002<br>terry : 11/21/2002<br>alopez : 9/7/2001<br>terry : 9/4/2001<br>jlewis : 8/2/1999<br>jlewis : 8/2/1999<br>jlewis : 7/30/1999<br>terry : 7/15/1999<br>terry : 1/6/1999<br>alopez : 7/17/1998<br>terry : 7/17/1998<br>terry : 6/4/1998<br>terry : 5/21/1998<br>carol : 3/21/1998<br>mark : 3/1/1998<br>mark : 12/1/1997<br>mark : 12/1/1997<br>mark : 12/1/1997
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<strong>*</strong> 602136
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PEROXISOME BIOGENESIS FACTOR 1; PEX1
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<em>Alternative titles; symbols</em>
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PEROXIN 1
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<strong><em>HGNC Approved Gene Symbol: PEX1</em></strong>
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<strong>SNOMEDCT:</strong> 238062008;
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<strong>ICD10CM:</strong> G60.1;
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Cytogenetic location: 7q21.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:92,487,025-92,528,520 </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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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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7q21.2
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Heimler syndrome 1
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234580
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Autosomal recessive
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3
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Peroxisome biogenesis disorder 1A (Zellweger)
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214100
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Autosomal recessive
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3
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Peroxisome biogenesis disorder 1B (NALD/IRD)
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601539
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Autosomal recessive
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3
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<strong>TEXT</strong>
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<strong>Cloning and Expression</strong>
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<p>Reuber et al. (1997) and Portsteffen et al. (1997) identified the human ortholog of yeast PEX1, a gene required for peroxisomal matrix protein import. The gene encodes a 147-kD member of the AAA protein family (ATPases associated with diverse cellular activities). </p><p>By functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO) cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged 'enhanced' green fluorescent protein, Tamura et al. (1998) isolated a human PEX1 cDNA. This cDNA encoded a hydrophilic protein comprising 1,283 amino acids, with high homology to the AAA-type ATPase family. A stable transformant of ZP107 with human PEX1 was morphologically and biochemically restored for peroxisome biogenesis. </p>
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<strong>Gene Structure</strong>
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<p>Portsteffen et al. (1997) detected 24 exons in the human PEX1 gene. </p>
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<strong>Mapping</strong>
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<span class="mim-text-font">
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<p>By computer-based 'homology probing' using the yeast sequence to screen a database of expressed sequence tags (dbEST) for human cDNA clones, Portsteffen et al. (1997) found a contig sequence localized to 7q21-q22 that exactly matched their cDNA. They identified the human PEX1 homolog and characterized its exon/intron structure. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Peroxisome Biogenesis Disorders 1A and 1B</em></strong></p><p>
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Reuber et al. (1997) found that expression of human PEX1 restored peroxisomal protein import in fibroblasts from 30 patients with peroxisomal biogenesis disorders of complementation group 1 (CG1; see PBD1A, 214100). Additionally, they detected PEX1 mutations in multiple CG1 probands. A common PEX1 allele, gly843-to-asp (G843D; 602136.0001), was present in approximately half of the CG1 patients and was shown to have a deleterious effect on PEX1 activity. Phenotypic analysis of PEX1-deficient cells revealed severe defects in peroxisomal matrix protein import and destabilization of PEX5 (600414), the receptor for the type 1 peroxisomal targeting signal, even though peroxisomes were present in these cells and capable of importing peroxisomal membrane proteins. These data demonstrated an important role for PEX1 in peroxisome biogenesis and suggested that mutations in PEX1 are the most common cause of the peroxisomal biogenesis disorders (see 601539). Homozygosity for the G843D mutation was found in patients with peroxisome biogenesis disorder-1B (PBD1B; 601539), including at least 1 individual exhibiting neonatal adrenoleukodystrophy (NALD) as well as several cases of infantile Refsum disease (IRD). Heterozygosity for the G843D mutation (with other alleles not characterized) was found in cases of NALD, IRD, and Zellweger syndrome (ZS; 214100) (Reuber et al., 1997). These 3 disorders appeared to represent a continuum of clinical features that are most severe in ZS, milder in NALD, and least severe in IRD. </p><p>Portsteffen et al. (1997) identified 3 mutant alleles in CG1 patients, including the G843D mutation, which was found in homozygosity in 1 patient and heterozygosity in another. </p><p>Tamura et al. (1998) demonstrated that human PEX1 expression restored peroxisomal protein import in fibroblasts from 3 patients with Zellweger syndrome and neonatal adrenoleukodystrophy of complementation group 1, which is the peroxisome biogenesis disorder (PBD) of highest incidence. Tamura et al. (1998) found that a patient with Zellweger syndrome was compound heterozygous for inactivating mutations of the PEX1 gene (602136.0002, 602136.0003). The cDNAs corresponding to these PEX1 mutations were defective in peroxisome-restoring activity when expressed in the patient's fibroblasts as well as in ZP107 cells. This method of identifying PEX1 cDNA complements that used by Reuber et al. (1997) and Portsteffen et al. (1997), who isolated the human PEX1 gene by a homology search of a human EST database using a yeast PEX1 sequence. All 3 studies demonstrated unequivocally that PEX1 is the causative gene for complementation group 1 peroxisomal disorders. </p><p>In fibroblasts from all CG1 infantile Refsum disease (IRD) patients examined, Imamura et al. (1998) found that peroxisomes were morphologically and biochemically formed at 30 degrees centigrade but not at 37 degrees centigrade; on the other hand, almost no peroxisomes were seen in Zellweger syndrome and neonatal adrenoleukodystrophy cells, even at 30 degrees centigrade. The mutation G843D (602136.0001) was found in the PEX1 allele of most CG1 IRD patients. The mutant PEX1 G843D gave rise to the same temperature-sensitive phenotype on CG1 CHO cell mutants upon transfection. Collectively, these results demonstrated temperature-sensitive peroxisome assembly to be responsible for the mildness of the clinical features of PEX1-defective IRD of complementation group 1. Imamura et al. (1998) suggested that the severity of peroxisome biogenesis disorder can be prognosticated by examining the temperature-sensitive complementation of peroxisomes in patient fibroblasts. This prognostic tool may encourage pediatricians to treat the milder PBD variants with therapies such as an oral administration of docosahexaenoic acid. </p><p>Collins and Gould (1999) analyzed all 24 exons of the PEX1 gene in 4 patients with CG1 Zellweger syndrome, including 2 patients in whom Gartner et al. (1992) had found variants in the PMP70 gene (170995.0001, 170995.0002). PEX1 mutations were detected in all 4 patients, including a 1-bp insertion (2097insT; 602136.0004) in exon 13 that was present in 3 of the 4 patients. Screening for the 2097insT mutation in 32 additional CG1 patients revealed 3 who were homozygous and 12 who were heterozygous for the insertion. Collins and Gould (1999) noted that in contrast to the other common PEX1 mutation, G843D, which is associated with a trend toward the mild end of the ZS phenotypic spectrum, this second common PEX1 mutation is associated with severe phenotypes. </p><p>Mutations in PEX1 account for approximately 65% of patients with PBDs. Walter et al. (2001) found that complete lack of PEX1 protein is associated with severe Zellweger syndrome; however, residual amounts of PEX1 protein were found in patients with the milder phenotypes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD). Most of the IRD patients carried at least 1 copy of the common G843D allele. When patient fibroblasts harboring this allele were grown at 30 degrees centigrade, a 2- to 3-fold increase in PEX1 protein levels was observed, associated with the recovery of peroxisomal function. This suggested that the G843D missense mutation results in a misfolded protein, which is more stable at lower temperatures. Walter et al. (2001) concluded that their search for the factors and/or mechanisms that determine the stability of mutant PEX1 proteins can be a first step in the development of therapeutic strategies for patients with mild PBDs. </p><p>In the subgroup of PBD patients with ZS, NALD, and IRD, more than half have mutations in the PEX1 gene. Maxwell et al. (2002) identified 5 novel mutations in an Australasian cohort of PEX1-deficient PBD patients, including a frameshift mutation in exon 18 (602136.0005) that was present in moderately high frequency (approximately 10% of alleles). </p><p>Majewski et al. (2011) identified biallelic mutations in the PEX1 gene in 2 patients. Patient 1 was a 28-year-old woman with PBD1B who had normal cognition and a history of Leber congenital amaurosis (LCA; see 204000). She was homozygous for the common G843D mutation (602136.0001). Patient 2 was an infant with PBD1A who presented with LCA at 9 months of age and had developmental delay, hypotonia, and seizures at 20 months of age. She was compound heterozygous for the G843D mutation and a 1-bp insertion (c.2098insT; 602136.0010). </p><p><strong><em>Heimler Syndrome 1</em></strong></p><p>
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In affected individuals from 4 unrelated families with sensorineural hearing loss, enamel hypoplasia, and nail defects (HMLR1; 234580), Ratbi et al. (2015) identified biallelic mutations in the PEX1 gene (602136.0004 and 602136.0006-602136.0009). The authors noted that in contrast to patients with PBDs at the severe end of the clinical spectrum, these patients showed no identifiable dysmorphic or additional neurologic features. Complementation assays in PEX1-null cells transfected with variants from patients with Heimler syndrome-1 demonstrated that all affected individuals had at least 1 PEX variant with residual activity in peroxisomal biogenesis. </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>Genotype/Phenotype Correlations</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>Maxwell et al. (2002) found a close correlation between cellular phenotype, disease severity, and PEX1 genotype in an Australasian cohort of PEX1-deficient PBD patients. Preuss et al. (2002) also found a close correlation between PEX1 genotype and age of survival in 16 well-documented Zellweger spectrum patients, which supported the usefulness of determining the exact PEX1 mutations in patients. Missense mutations caused milder disease, while insertions, deletions, and nonsense mutations were associated with severe clinical disease. </p><p>In 21 of 31 patients with PBDs, Poll-The et al. (2004) identified mutations in the PEX1 gene. The most common mutations were G843D (602136.0001) and 2097insT (602136.0004), which were associated with mild and severe Zellweger syndrome, respectively. Patients homozygous for G843D tended to have a better developmental outcome than did patients compound heterozygous for the 2 mutations. However, there were exceptions, suggesting that unknown factors influence the ultimate phenotype. </p><p>In a study of 168 Zellweger spectrum patients, including 33 of their own, Rosewich et al. (2005) found that the G843D and 2097insT mutations accounted for over 80% of all abnormal PEX1 alleles. Most of the mutations were distributed over the 2 AAA cassettes with the 2 functional protein domains, D1 and D2, and the highly conserved Walker motifs. PEX1 mutations could be divided into 2 classes: class I mutations led to residual PEX1 protein levels and function and a milder phenotype; class II mutations almost abolished PEX1 protein levels and function, resulting in a severe phenotype. Patients who were compound heterozygous for a class I and a class II mutation had an intermediate phenotype. </p><p>Crane et al. (2005) provided a detailed review of the mutations identified in the PEX1 gene. Mutations that produce premature termination codons are distributed throughout the PEX1 gene, whereas the majority of missense mutations segregate with the 2 essential AAA domains of the PEX1 protein. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>10 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 PEROXISOME BIOGENESIS DISORDER 1B</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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PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER), INCLUDED
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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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PEX1, GLY843ASP
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<br />
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SNP: rs61750420,
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gnomAD: rs61750420,
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ClinVar: RCV000007946, RCV000022416, RCV000032927, RCV000078922, RCV000345695, RCV000661947, RCV000763596, RCV000791271, RCV001004322, RCV001074120, RCV001266794, RCV001376560, RCV001731280, RCV003398462, RCV004786245
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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 patients with peroxisome biogenesis disorder-1B (PBD1B; 601539), including at least 1 individual exhibiting neonatal adrenoleukodystrophy (NALD) as well as several cases of infantile Refsum disease (IRD), Reuber et al. (1997) identified homozygosity for a gly843-to-asp (G843D) substitution in the PEX1 gene. In addition, the mutation was found in heterozygous state in cases of NALD, IRD, and Zellweger syndrome (PBD1A; 214100), with the other alleles uncharacterized. Functional analysis in patient fibroblasts suggested that the G843D mutant was only about 15% as active as wildtype PEX1. Portsteffen et al. (1997) also identified this mutation in homozygous and heterozygous state in patients with peroxisome biogenesis disorders of complementation group 1. </p><p>Among 23 German patients with peroxisomal biogenesis disorder of complementation group 1, Gartner et al. (1999) found that 8 were either homozygous or heterozygous for a c.2528G-A transition in exon 15 of PEX1, producing a G843D amino acid substitution. </p><p>In a 28-year-old woman (patient 1) with PBD1B, Majewski et al. (2011) identified homozygosity for the G843D mutation in the PEX1 gene. The mutation, which was identified by next-generation sequencing and confirmed by Sanger sequencing, was present in the carrier state in the parents. The patient had normal cognition and a history of Leber congenital amaurosis (LCA; see 204000). </p><p>In a patient (patient 2) with PBD1A, Majewski et al. (2011) identified compound heterozygous mutations in the PEX1 gene: G843D and a 1-bp insertion (c.2098insT; 602136.0010), resulting in a frameshift and premature termination (Ile700TyrfsTer42). The G843D mutation was identified by restriction enzyme analysis in a cohort of patients with LCA, and the c.2098insT mutation was identified by Sanger sequencing of the PEX1 gene. The patient presented with LCA at 9 months of age and had developmental delay, hypotonia, and seizures at 20 months of age. </p><p>Waterham and Ebberink (2012) noted that the G843D mutation reduces the binding between PEX1 and PEX6 (601498). The effect of the mutation is relatively mild, and cells of patients with this mutation often display peroxisomal mosaicism when cultured at 37 degrees Celsius. </p><p>Waterham and Ebberink (2012) noted that mutations in the PEX1 gene have a frequency of 58.9% among patients with Zellweger spectrum disorders. Steinberg et al. (2006) gave the allele frequency of the G843D mutation as 0.43, making it the most common mutation in PEX1-deficient 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>.0002 PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER)</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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PEX1, LEU664PRO
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<br />
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SNP: rs121434455,
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ClinVar: RCV000007949, RCV000763597, RCV001248383, RCV003473054, RCV003480024
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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 patient with Zellweger syndrome of complementation group 1 (PBD1A; 214100), Tamura et al. (1998) identified compound heterozygosity for a 1191T-C mutation in the PEX1 gene, resulting in an leu664-to-pro (L664P) substitution, and a 171-bp deletion of nucleotide residues 1,900 to 2,070 (602136.0003). Northern blot analysis of patient and control mRNA revealed a 4.3-kb band in both, suggesting that PEX1 transcription was unaffected in the patient. Functional analysis demonstrated that cDNAs corresponding to both PEX1 mutations were defective in peroxisome-restoring activity when expressed in the patient's fibroblasts as well as in ZP107 cells. </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>
|
|
<span class="mim-font">
|
|
<strong>.0003 PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER)</strong>
|
|
</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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PEX1, 171-BP DEL
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<br />
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SNP: rs1554372074,
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ClinVar: RCV000007951
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>For discussion of the 171-bp deletion of nucleotide residues 1,900 to 2,070 in the PEX1 gene that was found in compound heterozygous state in a patient with Zellweger syndrome of complementation group A (PBD1A; 214100) by Tamura et al. (1998), see 602136.0002. </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>
|
|
<span class="mim-font">
|
|
<strong>.0004 PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER)</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
HEIMLER SYNDROME 1, INCLUDED
|
|
</span>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
PEX1, 1-BP INS, 2097T
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<br />
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|
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SNP: rs61750415,
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|
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gnomAD: rs61750415,
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|
|
ClinVar: RCV000007953, RCV000078918, RCV000201307, RCV000500705, RCV000850579, RCV000853332, RCV001004324, RCV001073754, RCV001376645, RCV002512885, RCV003415676, RCV004814857
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|
|
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|
|
</span>
|
|
</div>
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 patients with Zellweger syndrome (PBD1A; 214100), including a severely affected patient who was studied by Gartner et al. (1992) (patient PBD002) and another patient in whom Reuber et al. (1997) had identified a PEX1 splice donor mutation, Collins and Gould (1999) identified homozygosity or compound heterozygosity for a 1-bp insertion (c.2097insT) in exon 13 of the PEX1 gene. Screening for 2097insT in 32 additional CG1 patients revealed that 3 were homozygous and 12 heterozygous for the insertion. The authors concluded that 2097insT is a common allele in the CG1 patient population, and noted that in contrast to the other common mutation, G843D (602136.0001), which is associated with a trend toward the mild end of the ZS phenotypic spectrum, this second common PEX1 mutation is associated with severe phenotypes. </p><p>Steinberg et al. (2006) gave the allele frequency of this mutation as 0.35 in PEX1-deficient patients. </p><p>In a brother and sister with Heimler syndrome-1 (HMLR1; 234580), originally reported by Heimler et al. (1991), Ratbi et al. (2015) identified compound heterozygosity for the c.2097dupT mutation (c.2097dupT, NM_000466.2) in the PEX1 gene and a c.2114T-G transversion, resulting in a leu705-to-trp (L705W; 602136.0006) substitution. In an unrelated 24-year-old woman with HMLR1, they identified compound heterozygosity for the 2097dupT mutation and a c.1742G-C transversion, resulting in an arg581-to-pro (R581P; 602136.0007) substitution. The mutations segregated with disease in both families, and were not found in 770 in-house exomes; in addition, the L705W mutation was not found in public databases, whereas the R581P mutation was present in 1 of 121,398 alleles in the ExAC Browser (minor allele frequency less than 0.000033). The 3 affected individuals all had sensorineural hearing loss, enamel hypoplasia, and nail defects, but did not exhibit dysmorphism or additional neurologic features. Complementation assays in transfected PEX1-null cells demonstrated that the c.2097dupT variant resulted in no complementation, whereas transfection with the c.1742G-C and c.2114T-G variants rescued peroxisomal biogenesis in 23% and 58% of cells, respectively. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
PEROXISOME BIOGENESIS DISORDER 1B, INCLUDED
|
|
</span>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PEX1, 1-BP DEL, 2916A
|
|
|
|
|
|
<br />
|
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|
|
SNP: rs61750426,
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|
|
gnomAD: rs61750426,
|
|
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|
|
|
ClinVar: RCV000169435, RCV000414630, RCV000588350, RCV001004318, RCV001201389, RCV002470783, RCV003474914, RCV005042357
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among 72 mutant alleles from Australasian patients with Zellweger syndrome (ZS; 214100), neonatal adrenoleukodystrophy (NALD; see 601539), and infantile Refsum disease (see 601539), Maxwell et al. (2002) found that 7 (9.7%) had a 1-bp deletion, 2916delA, in exon 18 of the PEX1 gene, causing a frameshift mutation after gly973 and resulting in nonsense-mediated mRNA decay. The mutation resulted in complete loss of PEX1 function and was associated with a severe Zellweger syndrome phenotype. This was the third most common mutation in this cohort after the G843D (602136.0001) and exon 13 frameshift (602136.0004) mutations. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HEIMLER SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PEX1, LEU705TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs863225084,
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|
|
|
|
|
gnomAD: rs863225084,
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|
|
|
|
|
ClinVar: RCV000201290, RCV001075286, RCV001810437, RCV002517304, RCV003417729, RCV004701263
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.2114T-G transversion (c.2114T-G, NM_000466.2) in the PEX1 gene, resulting in a leu705-to-trp (L705W) substitution, that was found in compound heterozygous state in 2 sibs with Heimler syndrome-1 (HMLR1; 234580) by Ratbi et al. (2015), see 602136.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 HEIMLER SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PEX1, ARG581PRO
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs370483961,
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|
|
gnomAD: rs370483961,
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|
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ClinVar: RCV000201302, RCV001075087, RCV001377625, RCV002500626
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.1742G-C transversion (c.1742G-C, NM_000466.2) in the PEX1 gene, resulting in an arg581-to-pro (R581P) substitution, that was found in compound heterozygous state in 2 unrelated patients with Heimler syndrome-1 (HMLR1; 234580) by Ratbi et al. (2015), see 602136.0004 and 602136.0008. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 HEIMLER SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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|
|
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<div>
|
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<span class="mim-text-font">
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PEX1, IVS5, G-T, +1
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<br />
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SNP: rs756876301,
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gnomAD: rs756876301,
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ClinVar: RCV000201308, RCV000633316, RCV001004518, RCV001376605, RCV001526999, RCV001795328, RCV003422106, RCV005031756
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 19-year-old Irish woman with sensorineural hearing loss, enamel hypoplasia, and nail defects (HMLR1; 234580), Ratbi et al. (2015) identified compound heterozygosity for a splice site mutation (c.1239+1G-T, NM_000466.2) in intron 5 of the PEX1 gene, and a c.1742G-C transversion resulting in an arg581-to-pro (R581P; 602136.0007) substitution. Ratbi et al. (2015) noted that the intron 5 splice site mutation had been identified in compound heterozygosity with a PEX1 frameshift mutation in a patient with a peroxisome biogenesis disorder in the Zellweger syndrome spectrum (see PBD1A, 214100) by Yik et al. (2009). Yik et al. (2009) reported no clinical information for the patient with the Zellweger spectrum disorder, but Ratbi et al. (2015) stated that the Irish patient did not exhibit dysmorphism or additional neurologic features. The mutations segregated with disease in the family. The previously unreported c.1742G-C mutation was not found in 770 in-house exomes but was present in 1 of 121,398 alleles in the ExAC Browser (minor allele frequency less than 0.000033). Complementation assays in PEX1-null cells demonstrated that transfection with the c.1742G-C variant rescued peroxisomal biogenesis in 23% of cells. </p>
|
|
</span>
|
|
</div>
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|
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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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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 HEIMLER SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
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PEX1, TRP1250TER
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<br />
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SNP: rs863225085,
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ClinVar: RCV000201292
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Moroccan sister and brother with sensorineural hearing loss, enamel hypoplasia, and nail defects (HMLR1; 234580), Ratbi et al. (2015) identified homozygosity for a c.3750G-A transition (c.3750G-A, NM_000466.2) in exon 23 of the PEX1 gene, resulting in a trp1250-to-ter (W1250X) substitution. The mutation segregated with disease in the family and was not found in 250 ethnically matched controls, 770 in-house exomes, or in public databases. Analysis of patient plasma, erythrocytes, and fibroblasts did not show any peroxisomal biochemical aberrations, consistent with their relatively very mild disease; however, immunofluorescence microscopy of patient fibroblasts revealed a mosaic peroxisomal pattern similar to that previously associated with hypomorphic variants. Complementation assays in PEX1-null cells demonstrated that transfection with the c.3750G-A variant rescued peroxisomal biogenesis in approximately 30% of cells. </p>
|
|
</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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<span class="mim-font">
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<strong>.0010 PEROXISOME BIOGENESIS DISORDER 1A (ZELLWEGER)</strong>
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</h4>
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PEX1, 1-BP INS, 2098T
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<br />
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ClinVar: RCV000007953, RCV000078918, RCV000201307, RCV000500705, RCV000850579, RCV000853332, RCV001004324, RCV001073754, RCV001376645, RCV002512885, RCV003415676, RCV004814857
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<p>For discussion of the 1-bp insertion (c.2098insT) in the PEX1 gene, resulting in a frameshift and premature termination (Ile700TyrfsTer42), that was found in compound heterozygous state in a patient with peroxisome biogenesis disorder-1A (PBD1A; 214100) by Majewski et al. (2011), see 602136.0001. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Collins, C. S., Gould, S. J.
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<strong>Identification of a common PEX1 mutation in Zellweger syndrome.</strong>
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Hum. Mutat. 14: 45-53, 1999.
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[PubMed: 10447258]
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[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Crane, D. I., Maxwell, M. A., Paton, B. C.
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<strong>PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders.</strong>
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Hum. Mutat. 26: 167-175, 2005.
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[PubMed: 16086329]
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[Full Text: https://doi.org/10.1002/humu.20211]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gartner, J., Moser, H., Valle, D.
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<strong>Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome.</strong>
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Nature Genet. 1: 16-23, 1992.
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[PubMed: 1301993]
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[Full Text: https://doi.org/10.1038/ng0492-16]
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<p class="mim-text-font">
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Gartner, J., Preuss, N., Brosius, U., Biermanns, M.
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<strong>Mutations in PEX1 in peroxisome biogenesis disorders: G843D and a mild clinical phenotype.</strong>
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J. Inherit. Metab. Dis. 22: 311-313, 1999.
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[PubMed: 10384394]
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[Full Text: https://doi.org/10.1023/a:1005599903632]
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<p class="mim-text-font">
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Heimler, A., Fox, J. E., Hershey, J. E., Crespi, P.
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<strong>Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs.</strong>
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Am. J. Med. Genet. 39: 192-195, 1991.
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[PubMed: 2063923]
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[Full Text: https://doi.org/10.1002/ajmg.1320390214]
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</p>
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<p class="mim-text-font">
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Imamura, A., Tamura, S., Shimozawa, N., Suzuki, Y., Zhang, Z., Tsukamoto, T., Orii, T., Kondo, N., Osumi, T., Fujiki, Y.
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<strong>Temperature-sensitive mutation in PEX1 moderates the phenotypes of peroxisome deficiency disorders.</strong>
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Hum. Molec. Genet. 7: 2089-2094, 1998.
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[PubMed: 9817926]
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[Full Text: https://doi.org/10.1093/hmg/7.13.2089]
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</p>
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<li>
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<p class="mim-text-font">
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Majewski, J., Wang, Z., Lopez, I., Al Humaid, S., Ren, H., Racine, J., Bazinet, A., Mitchel, G., Braverman, N., Koenekoop, R. K.
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<strong>A new ocular phenotype associated with an unexpected but known systemic disorder and mutation: novel use of genomic diagnostics and exome sequencing.</strong>
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J. Med. Genet. 48: 593-596, 2011.
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[PubMed: 21862673]
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[Full Text: https://doi.org/10.1136/jmedgenet-2011-100288]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Maxwell, M. A., Allen, T., Solly, P. B., Svingen, T., Paton, B. C., Crane, D. I.
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<strong>Novel PEX1 mutations and genotype-phenotype correlations in Australasian peroxisome biogenesis disorder patients.</strong>
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Hum. Mutat. 20: 342-351, 2002.
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[PubMed: 12402331]
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[Full Text: https://doi.org/10.1002/humu.10128]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Poll-The, B. T., Gootjes, J., Duran, M., de Klerk, J. B. C., Maillette de Buy Wenniger-Prick, L. J., Admiraal, R. J. C., Waterham, H. R., Wanders, R. J. A., Barth, P. G.
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<strong>Peroxisome biogenesis disorders with prolonged survival: phenotypic expression in a cohort of 31 patients.</strong>
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Am. J. Med. Genet. 126A: 333-338, 2004.
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[PubMed: 15098231]
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[Full Text: https://doi.org/10.1002/ajmg.a.20664]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., Dodt, G.
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<strong>Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders.</strong>
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Nature Genet. 17: 449-452, 1997.
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[PubMed: 9398848]
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[Full Text: https://doi.org/10.1038/ng1297-449]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Preuss, N., Brosius, U., Biermanns, M., Muntau, A. C., Conzelmann, E., Gartner, J.
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<strong>PEX1 mutations in complementation group 1 of Zellweger spectrum patients correlate with severity of disease.</strong>
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Pediat. Res. 51: 706-714, 2002.
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[PubMed: 12032265]
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[Full Text: https://doi.org/10.1203/00006450-200206000-00008]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqaih, N., Guaoua, S., Vandeweyer, G., Urquhart, J. E., Chandler, K. E., Williams, S. G., Roberts, N. A., El Alloussi, M., Black, G. C., and 19 others.
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<strong>Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6.</strong>
|
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Am. J. Hum. Genet. 97: 535-545, 2015.
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[PubMed: 26387595]
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[Full Text: https://doi.org/10.1016/j.ajhg.2015.08.011]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., Valle, D., Gould, S. J.
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<strong>Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.</strong>
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Nature Genet. 17: 445-448, 1997.
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[PubMed: 9398847]
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[Full Text: https://doi.org/10.1038/ng1297-445]
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</p>
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<p class="mim-text-font">
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Rosewich, H., Ohlenbusch, A., Gartner, J.
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<strong>Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations.</strong>
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J. Med. Genet. 42: e58, 2005. Note: Electronic Article.
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[PubMed: 16141001]
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[Full Text: https://doi.org/10.1136/jmg.2005.033324]
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<p class="mim-text-font">
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Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., Moser, H. W.
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<strong>Peroxisome biogenesis disorders.</strong>
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[PubMed: 17055079]
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[Full Text: https://doi.org/10.1016/j.bbamcr.2006.09.010]
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<p class="mim-text-font">
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Tamura, S., Okumoto, K., Toyama, R., Shimozawa, N., Tsukamoto, T., Suzuki, Y., Osumi, T., Kondo, N., Fujiki, Y.
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<strong>Human PEX1 cloned by functional complementation in a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.</strong>
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Proc. Nat. Acad. Sci. 95: 4350-4355, 1998.
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[PubMed: 9539740]
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Walter, C., Gootjes, J., Mooijer, P. A., Portsteffen, H., Klein, C., Waterham, H. R., Barth, P. G., Epplen, J. T., Kunau, W.-H., Wanders, R. J. A., Dodt, G.
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<strong>Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels.</strong>
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[PubMed: 11389485]
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Waterham, H. R., Ebberink, M. S.
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<strong>Genetics and molecular basis of human peroxisome biogenesis disorders.</strong>
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Yik, W. Y., Steinberg, S. J., Moser, A. B., Moser, H. W., Hacia, J. G.
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<strong>Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders.</strong>
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Hum. Mutat. 30: E467-E480, 2009. Note: Electronic Article.
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[PubMed: 19105186]
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To ensure long-term funding for the OMIM project, we have diversified
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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