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Entry
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- *611026 - FATTY ACID 2-HYDROXYLASE; FA2H
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- OMIM
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<p>
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<span class="h4">*611026</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/611026">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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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<h4 class="panel-title">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</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=ENSG00000103089;t=ENST00000219368" 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=79152" 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=611026" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</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=ENSG00000103089;t=ENST00000219368" 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_024306,XM_011523317,XM_011523319" 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_024306" 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=611026" 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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<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=16873&isoform_id=16873_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/FA2H" 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/3219336,12053843,16554016,52632409,52632414,52790417,74749893,119616083,119616084,189054909,205360949,221044790,767990511,767990515,2462550741,2462550743" 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/Q7L5A8" 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 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=79152" 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=ENSG00000103089;t=ENST00000219368" 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=FA2H" 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=FA2H" 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+79152" 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/FA2H" 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:79152" 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/79152" 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=chr16&hgg_gene=ENST00000219368.8&hgg_start=74712969&hgg_end=74774820&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 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:21197" 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:21197" 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/fa2h" 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=611026[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 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=611026[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/FA2H/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000103089" 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=FA2H" 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=FA2H" 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=FA2H" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FA2H&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/PA145148065" 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:21197" 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/FBgn0050502.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:2443327" 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/FA2H#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:2443327" 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/79152/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002450/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=79152" 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=WBGene00007707;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-031219-4" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=FA2H&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> 764688002<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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611026
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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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FATTY ACID 2-HYDROXYLASE; FA2H
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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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FATTY ACID ALPHA-HYDROXYLASE; FAAH<br />
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FATTY ACID HYDROXYLASE DOMAIN-CONTAINING PROTEIN 1; FAXDC1<br />
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FAH1, S. CEREVISIAE, HOMOLOG OF; FAH1<br />
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SCS7, S. CEREVISIAE, HOMOLOG OF; SCS7
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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=FA2H" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FA2H</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/16/640?start=-3&limit=10&highlight=640">16q23.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr16:74712969-74774820&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'})">16:74,712,969-74,774,820</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/16/640?start=-3&limit=10&highlight=640">
|
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16q23.1
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
Spastic paraplegia 35, autosomal recessive
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/612319"> 612319 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/611026" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/611026" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<p>Sphingolipids are a large class of lipids found in all eukaryotic cells and are involved in numerous cellular processes. The structural diversity of sphingolipids stems from more than 300 distinct head groups, as well as from modifications of the hydrophobic ceramide moiety. FA2H catalyzes a common modification of the ceramide moiety: hydroxylation at the 2 position of the N-acyl chain. Sphingolipids containing 2-hydroxy fatty acid are common in nervous and epidermal tissue. Glycosphingolipids containing a high proportion of 2-hydroxy fatty acid are critical components of myelin, and several very long chain ceramides with 2-hydroxy fatty acids are important for the permeability barrier function of epidermis (summary by <a href="#1" class="mim-tip-reference" title="Alderson, N. L., Rembiesa, B. M., Walla, M. D., Bielawska, A., Bielawski, J., Hama, H. <strong>The human FA2H gene encodes a fatty acid 2-hydroxylase.</strong> J. Biol. Chem. 279: 48562-48568, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15337768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15337768</a>] [<a href="https://doi.org/10.1074/jbc.M406649200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15337768">Alderson et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15337768" 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 searching databases for homologs of yeast Fah1, <a href="#1" class="mim-tip-reference" title="Alderson, N. L., Rembiesa, B. M., Walla, M. D., Bielawska, A., Bielawski, J., Hama, H. <strong>The human FA2H gene encodes a fatty acid 2-hydroxylase.</strong> J. Biol. Chem. 279: 48562-48568, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15337768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15337768</a>] [<a href="https://doi.org/10.1074/jbc.M406649200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15337768">Alderson et al. (2004)</a> identified human FA2H. The deduced 372-amino acid protein has a calculated molecular mass of 42.8 kD and shares 36% identity with yeast Fah1. FA2H contains an N-terminal cytochrome b5 (<a href="/entry/613218">613218</a>) domain, 4 transmembrane domains, and an iron-binding histidine motif conserved among membrane-bound desaturases and hydroxylases. Northern blot analysis showed highest expression of a 3-kb transcript in brain and colon, with lower levels in testis, prostate, pancreas, and kidney. FA2H was detected exclusively in the membrane fraction of transfected COS-7 cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15337768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Eckhardt, M., Yaghootfam, A., Fewou, S. N., Zoller, I., Gieselmann, V. <strong>A mammalian fatty acid hydroxylase responsible for the formation of alpha-hydroxylated galactosylceramide in myelin.</strong> Biochem. J. 388: 245-254, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15658937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15658937</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15658937[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/10.1042/BJ20041451" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15658937">Eckhardt et al. (2005)</a> identified mouse Fa2h. Both mouse and human FA2H have a C-terminal endoplasmic reticulum (ER) retention motif, and immunofluorescence analysis showed that mouse Fa2h colocalized with calnexin (CANX; <a href="/entry/114217">114217</a>), an ER marker protein, in transfected Chinese hamster ovary cells. Northern blot analysis detected Fa2h expression in mouse brain, stomach, skin, kidney, testis, and small intestine. In mouse brain, Fa2h expression increased strongly between 1 and 2 weeks of age, reached maximal level between 2 and 3 weeks of age, and decreased slightly in older animals. In situ hybridization of mouse brain showed highest expression in white matter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15658937" 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="#6" class="mim-tip-reference" title="Kruer, M. C., Paisan-Ruiz, C., Boddaert, N., Yoon, M. Y., Hama, H., Gregory, A., Malandrini, A., Woltjer, R. L., Munnich, A., Gobin, S., Polster, B. J., Palmeri, S., Edvardson, S., Hardy, J., Houlden, H., Hayflick, S. J. <strong>Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).</strong> Ann. Neurol. 68: 611-618, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20853438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20853438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20853438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.22122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20853438">Kruer et al. (2010)</a> stated that the FA2H gene maps to chromosome 16q23.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20853438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Eckhardt, M., Yaghootfam, A., Fewou, S. N., Zoller, I., Gieselmann, V. <strong>A mammalian fatty acid hydroxylase responsible for the formation of alpha-hydroxylated galactosylceramide in myelin.</strong> Biochem. J. 388: 245-254, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15658937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15658937</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15658937[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/10.1042/BJ20041451" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15658937">Eckhardt et al. (2005)</a> mapped the mouse Fa2h gene to chromosome 8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15658937" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Alderson, N. L., Rembiesa, B. M., Walla, M. D., Bielawska, A., Bielawski, J., Hama, H. <strong>The human FA2H gene encodes a fatty acid 2-hydroxylase.</strong> J. Biol. Chem. 279: 48562-48568, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15337768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15337768</a>] [<a href="https://doi.org/10.1074/jbc.M406649200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15337768">Alderson et al. (2004)</a> found that COS-7 cells expressing human FA2H had 3- to 20-fold higher levels of 2-hydroxyceramides and 2-hydroxy fatty acids compared with control cells, and they observed a 40-fold increase in 2-hydroxyceramides in cells incubated 72 hrs. Deletion of the cytochrome b5 domain sharply reduced FA2H enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15337768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RT-PCR and Western blot analysis, <a href="#8" class="mim-tip-reference" title="Uchida, Y., Hama, H., Alderson, N. L., Douangpanya, S., Wang, Y., Crumrine, D. A., Elias, P. M., Holleran, W. M. <strong>Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation.</strong> J. Biol. Chem. 282: 13211-13219, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17355976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17355976</a>] [<a href="https://doi.org/10.1074/jbc.M611562200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17355976">Uchida et al. (2007)</a> showed that FA2H was expressed in human keratinocytes and epidermis. FA2H expression and fatty acid 2-hydroxylase activity increased during differentiation. Downregulation of FA2H by small interfering RNA suppressed 2-hydroxylase activity and decreased levels of 2-hydroxyceramide and 2-hydroxyglucosylceramide in keratinocytes. <a href="#8" class="mim-tip-reference" title="Uchida, Y., Hama, H., Alderson, N. L., Douangpanya, S., Wang, Y., Crumrine, D. A., Elias, P. M., Holleran, W. M. <strong>Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation.</strong> J. Biol. Chem. 282: 13211-13219, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17355976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17355976</a>] [<a href="https://doi.org/10.1074/jbc.M611562200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17355976">Uchida et al. (2007)</a> demonstrated that 2-hydroxylation of fatty acid by FA2H occurred before formation of ceramides and glucosylceramides, and that these lipids were required for formation of epidermal lamellar membranes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17355976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of 2 unrelated consanguineous families with a complicated form of autosomal recessive spastic paraplegia (SPG35; <a href="/entry/612319">612319</a>), <a href="#5" class="mim-tip-reference" title="Edvardson, S., Hama, H., Shaag, A., Gomori, J. M., Berger, I., Soffer, D., Korman, S. H., Taustein, I., Saada, A., Elpeleg, O. <strong>Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.</strong> Am. J. Hum. Genet. 83: 643-648, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19068277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19068277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19068277[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.2008.10.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19068277">Edvardson et al. (2008)</a> identified a homozygous mutation in the FA2H gene (<a href="#0001">611026.0001</a>). The patients had early onset of progressive spasticity, ataxia, dystonia, and cognitive decline associated with white matter abnormalities on brain MRI. Affected individuals from a third family with a less severe phenotype were found to have a different homozygous mutation in the FA2H gene (<a href="#0002">611026.0002</a>). The relatively late onset of the disorders was consistent with the proposed need for FA2H at later stages of myelin maturation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19068277" 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 affected members of an Omani family and a Pakistani family with complicated SPG35, <a href="#2" class="mim-tip-reference" title="Dick, K. J., Eckhardt, M., Paisan-Ruiz, C., Alshehhi, A. A., Proukakis, C., Sibtain, N. A., Maier, H., Sharifi, R., Patton, M. A., Bashir, W., Koul, R., Raeburn, S., Gieselmann, V., Houlden, H., Crosby, A. H. <strong>Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35).</strong> Hum. Mutat. 31: E1251-1260, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20104589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20104589</a>] [<a href="https://doi.org/10.1002/humu.21205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20104589">Dick et al. (2010)</a> identified 2 different homozygous mutations in the FA2H gene (<a href="#0003">611026.0003</a> and <a href="#0004">611026.0004</a>, respectively). The findings indicated that mutations in FA2H are associated with SPG35, and that abnormal hydroxylation of myelin galactocerebroside lipid components can lead to a severe progressive phenotype, with a clinical presentation of complicated SPG and radiological features of leukodystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20104589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Kruer, M. C., Paisan-Ruiz, C., Boddaert, N., Yoon, M. Y., Hama, H., Gregory, A., Malandrini, A., Woltjer, R. L., Munnich, A., Gobin, S., Polster, B. J., Palmeri, S., Edvardson, S., Hardy, J., Houlden, H., Hayflick, S. J. <strong>Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).</strong> Ann. Neurol. 68: 611-618, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20853438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20853438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20853438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.22122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20853438">Kruer et al. (2010)</a> identified 2 different homozygous mutations in the FA2H gene (<a href="#0005">611026.0005</a> and <a href="#0006">611026.0006</a>) in affected members from 2 unrelated families with progressive complicated spastic paraplegia associated with brain iron deposition in the globus pallidus. The authors noted the connection between leukodystrophy and neurodegeneration with brain iron accumulation (NBIA). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20853438" 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="#9" class="mim-tip-reference" title="Zoller, I., Meixner, M., Hartmann, D, Bussow, H., Meyer, R., Gieselmann, V., Eckhardt, M. <strong>Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration.</strong> J. Neurosci. 28: 9741-9754, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18815260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18815260</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18815260[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/10.1523/JNEUROSCI.0458-08.2008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18815260">Zoller et al. (2008)</a> found that Fa2h-null mice lacked 2-hydroxylated sphingolipids in the brain and in peripheral nerves. However, nonhydroxylated galactosylceramide was increased, and oligodendrocyte differentiation, myelin formation, and peripheral nerve conduction velocities were normal up to 5 months of age. In contrast, aged 18-month-old Fa2h-null mice showed scattered axonal and myelin sheath degeneration in the spinal cord and more pronounced loss of myelin staining in sciatic nerves. These changes were associated with functional motor impairment. <a href="#9" class="mim-tip-reference" title="Zoller, I., Meixner, M., Hartmann, D, Bussow, H., Meyer, R., Gieselmann, V., Eckhardt, M. <strong>Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration.</strong> J. Neurosci. 28: 9741-9754, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18815260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18815260</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18815260[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/10.1523/JNEUROSCI.0458-08.2008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18815260">Zoller et al. (2008)</a> concluded that the long-term maintenance of myelin is impaired in the absence of 2-hydroxylated sphingolipids and suggested that these lipids might be required for glial support of axon function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18815260" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>8 Selected Examples</a>):</strong>
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<a href="/allelicVariants/611026" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=611026[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1567633766 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1567633766;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=rs1567633766" 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=rs1567633766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 7 affected members of 2 unrelated consanguineous Arab Muslim families with a complicated form of autosomal recessive spastic paraplegia (SPG35; <a href="/entry/612319">612319</a>), <a href="#5" class="mim-tip-reference" title="Edvardson, S., Hama, H., Shaag, A., Gomori, J. M., Berger, I., Soffer, D., Korman, S. H., Taustein, I., Saada, A., Elpeleg, O. <strong>Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.</strong> Am. J. Hum. Genet. 83: 643-648, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19068277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19068277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19068277[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.2008.10.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19068277">Edvardson et al. (2008)</a> identified a homozygous G-to-A transition in intron 5 of the FA2H gene, resulting in the skipping of exons 5 and 6 and predicted to abolish catalytic activity. The patients had early onset of progressive spasticity, ataxia, dystonia, and cognitive decline associated with white matter abnormalities on brain MRI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19068277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 sisters, from a consanguineous Arab Muslim family, with a complicated form of spastic paraplegia (SPG35; <a href="/entry/612319">612319</a>), <a href="#5" class="mim-tip-reference" title="Edvardson, S., Hama, H., Shaag, A., Gomori, J. M., Berger, I., Soffer, D., Korman, S. H., Taustein, I., Saada, A., Elpeleg, O. <strong>Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.</strong> Am. J. Hum. Genet. 83: 643-648, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19068277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19068277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19068277[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.2008.10.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19068277">Edvardson et al. (2008)</a> identified a homozygous 103G-T transversion in exon 1 of the FA2H gene, resulting in an asp35-to-tyr (D35Y) substitution. The patients had mild spasticity and difficulty walking, but did not have cerebellar signs, dystonia, or impaired cognition. Both unaffected parents were heterozygous for the mutation. In vitro expression studies showed that the transfected D35Y-mutant had enzyme activity indistinguishable from an empty vector, suggesting that the D35Y mutation inactivated FA2H. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19068277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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> rs387907039 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907039;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/rs387907039?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=rs387907039" 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=rs387907039" 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=RCV000023855 OR RCV001797590 OR RCV002509169" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023855, RCV001797590, RCV002509169" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023855...</a>
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<p>In affected members of a consanguineous Omani family with complicated autosomal recessive spastic paraplegia-35 (SPG35; <a href="/entry/612319">612319</a>), <a href="#2" class="mim-tip-reference" title="Dick, K. J., Eckhardt, M., Paisan-Ruiz, C., Alshehhi, A. A., Proukakis, C., Sibtain, N. A., Maier, H., Sharifi, R., Patton, M. A., Bashir, W., Koul, R., Raeburn, S., Gieselmann, V., Houlden, H., Crosby, A. H. <strong>Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35).</strong> Hum. Mutat. 31: E1251-1260, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20104589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20104589</a>] [<a href="https://doi.org/10.1002/humu.21205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20104589">Dick et al. (2010)</a> identified a homozygous 703C-T transition in exon 5 of the FA2H gene, resulting in an arg235-to-cys (R235C) substitution. The mutation was not found in 700 control chromosomes. In vitro functional expression studies showed that the mutation resulted in a reduction in hydroxylated ceramides to 60-80% of wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20104589" 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 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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> rs759947457 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs759947457;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/rs759947457?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=rs759947457" 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=rs759947457" 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=RCV000023856 OR RCV002293414 OR RCV002513206" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023856, RCV002293414, RCV002513206" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023856...</a>
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<p>In affected members of a consanguineous Pakistani family with complicated autosomal recessive spastic paraplegia-35 (SPG35; <a href="/entry/612319">612319</a>), <a href="#2" class="mim-tip-reference" title="Dick, K. J., Eckhardt, M., Paisan-Ruiz, C., Alshehhi, A. A., Proukakis, C., Sibtain, N. A., Maier, H., Sharifi, R., Patton, M. A., Bashir, W., Koul, R., Raeburn, S., Gieselmann, V., Houlden, H., Crosby, A. H. <strong>Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35).</strong> Hum. Mutat. 31: E1251-1260, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20104589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20104589</a>] [<a href="https://doi.org/10.1002/humu.21205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20104589">Dick et al. (2010)</a> identified a homozygous 18-bp deletion in exon 1 of the FA2H gene, resulting in the loss of 6 amino acids (53-58) in the cytochrome B5 domain of the protein. The mutation was not found in 200 control chromosomes. In vitro functional expression studies showed that the mutation resulted in undetectable levels of hydroxylated ceramides. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20104589" 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 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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> rs387907040 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907040;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/rs387907040?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=rs387907040" 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=rs387907040" 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=RCV000023857 OR RCV000483483 OR RCV002513207 OR RCV003317044" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023857, RCV000483483, RCV002513207, RCV003317044" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023857...</a>
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<p>In 3 Italian brothers, born of consanguineous parents, with a complicated form of autosomal recessive spastic paraplegia-35 (SPG35; <a href="/entry/612319">612319</a>) and evidence of brain iron accumulation in the globus pallidus, <a href="#6" class="mim-tip-reference" title="Kruer, M. C., Paisan-Ruiz, C., Boddaert, N., Yoon, M. Y., Hama, H., Gregory, A., Malandrini, A., Woltjer, R. L., Munnich, A., Gobin, S., Polster, B. J., Palmeri, S., Edvardson, S., Hardy, J., Houlden, H., Hayflick, S. J. <strong>Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).</strong> Ann. Neurol. 68: 611-618, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20853438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20853438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20853438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.22122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20853438">Kruer et al. (2010)</a> identified a homozygous 460C-T transition in exon 3 of the FA2H gene, resulting in an arg154-to-cys (R154C) substitution in a highly conserved residue. Western blot analysis of COS-7 cells transfected with the R154C mutation showed decreased FA2H protein levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20853438" 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 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE, WITH OR WITHOUT NEURODEGENERATION</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">rs587776891 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776891;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=rs587776891" 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=rs587776891" 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=RCV000023858 OR RCV002513208 OR RCV004700275" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023858, RCV002513208, RCV004700275" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023858...</a>
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<p>In 2 Albanian brothers with a complicated form of autosomal recessive spastic paraplegia-35 (SPG35; <a href="/entry/612319">612319</a>) and evidence of brain iron accumulation in the globus pallidus, <a href="#6" class="mim-tip-reference" title="Kruer, M. C., Paisan-Ruiz, C., Boddaert, N., Yoon, M. Y., Hama, H., Gregory, A., Malandrini, A., Woltjer, R. L., Munnich, A., Gobin, S., Polster, B. J., Palmeri, S., Edvardson, S., Hardy, J., Houlden, H., Hayflick, S. J. <strong>Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).</strong> Ann. Neurol. 68: 611-618, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20853438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20853438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20853438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.22122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20853438">Kruer et al. (2010)</a> identified a homozygous 2-bp deletion (c.509_510delAC) in the FA2H gene, resulting in a frameshift and premature termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20853438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Donkervoort, S., Dastgir, J., Hu, Y., Zein, W. M., Marks, H., Blackstone, C., Bonnemann, C. G. <strong>Phenotypic variability of a likely FA2H founder mutation in a family with complicated hereditary spastic paraplegia. (Letter)</strong> Clin. Genet. 85: 393-395, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23745665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23745665</a>] [<a href="https://doi.org/10.1111/cge.12185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23745665">Donkervoort et al. (2014)</a> identified homozygosity for the c.509_510delAC deletion in the FA2H gene, which resulted in a frameshift and a premature stop codon (Tyr170Ter), in a brother and sister from Montenegro with SPG35. The mutation segregated with the disorder in the family; functional studies were not performed. Both children had typical features of the disorder, but no brain iron accumulation was seen on brain MRI. Because this mutation had been identified by <a href="#6" class="mim-tip-reference" title="Kruer, M. C., Paisan-Ruiz, C., Boddaert, N., Yoon, M. Y., Hama, H., Gregory, A., Malandrini, A., Woltjer, R. L., Munnich, A., Gobin, S., Polster, B. J., Palmeri, S., Edvardson, S., Hardy, J., Houlden, H., Hayflick, S. J. <strong>Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).</strong> Ann. Neurol. 68: 611-618, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20853438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20853438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20853438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ana.22122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20853438">Kruer et al. (2010)</a> in 2 brothers from Albania with a similar neurodegenerative disorder with brain iron accumulation, <a href="#3" class="mim-tip-reference" title="Donkervoort, S., Dastgir, J., Hu, Y., Zein, W. M., Marks, H., Blackstone, C., Bonnemann, C. G. <strong>Phenotypic variability of a likely FA2H founder mutation in a family with complicated hereditary spastic paraplegia. (Letter)</strong> Clin. Genet. 85: 393-395, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23745665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23745665</a>] [<a href="https://doi.org/10.1111/cge.12185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23745665">Donkervoort et al. (2014)</a> suggested that it may represent a founder mutation in individuals from the Balkan region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23745665+20853438" 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>.0007 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE, WITH NEURODEGENERATION</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">rs387907172 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907172;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=rs387907172" 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=rs387907172" 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=RCV000024321" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024321" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024321</a>
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<p>In a 10-year-old boy, born of unrelated parents, with a complicated form of autosomal recessive spastic paraplegia-35 (SPG35; <a href="/entry/612319">612319</a>), <a href="#7" class="mim-tip-reference" title="Pierson, T. M., Simeonov, D. R., Sincan, M., Adams, D. A., Markello, T., Golas, G., Fuentes-Fajardo, K., Hansen, N. F., Cherukuri, P. F., Cruz, P., Mullikin, J. C., Blackstone, C., Tifft, C., Boerkoel, C. F., Gahl, W. A. <strong>Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration.</strong> Europ. J. Hum. Genet. 20: 476-479, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22146942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22146942</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22146942[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2011.222" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22146942">Pierson et al. (2012)</a> identified compound heterozygosity for a heterozygous 707T-C transition in exon 5 of the FA2H gene, resulting in a phe236-to-ser (F236S) substitution inherited from the unaffected father, and a 28-kb deletion encompassing exons 3 to 7 of the FA2H gene (<a href="#0008">611026.0008</a>) inherited from the unaffected mother. The F236S substitution occurred in a highly conserved residue in an iron-binding histidine motif in the catalytic site. The patient developed normally until age 3 years, when he developed progressive neurodegeneration following a febrile illness. He had lower extremity weakness and atrophy, spasticity, dystonic foot inversion, and poor balance. He also had dysarthria, neck weakness, mask-like facies, hunched posture, and mild cognitive deficits, but did not have optic atrophy or seizures. Serial brain MRIs showed progressive neurodegenerative changes, with white matter abnormalities, cerebellar and brainstem atrophy, thin corpus callosum, and evidence of demyelination. He also had an axonal sensory neuropathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22146942" 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 28-kb deletion in the FA2H gene that was found in compound heterozygous state in a patient with autosomal recessive spastic paraplegia-35 (SPG35; <a href="/entry/612319">612319</a>) by <a href="#7" class="mim-tip-reference" title="Pierson, T. M., Simeonov, D. R., Sincan, M., Adams, D. A., Markello, T., Golas, G., Fuentes-Fajardo, K., Hansen, N. F., Cherukuri, P. F., Cruz, P., Mullikin, J. C., Blackstone, C., Tifft, C., Boerkoel, C. F., Gahl, W. A. <strong>Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration.</strong> Europ. J. Hum. Genet. 20: 476-479, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22146942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22146942</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22146942[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2011.222" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22146942">Pierson et al. (2012)</a>, see <a href="#0007">611026.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22146942" 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>The human FA2H gene encodes a fatty acid 2-hydroxylase.</strong>
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J. Biol. Chem. 279: 48562-48568, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15337768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15337768</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15337768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Dick2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Dick, K. J., Eckhardt, M., Paisan-Ruiz, C., Alshehhi, A. A., Proukakis, C., Sibtain, N. A., Maier, H., Sharifi, R., Patton, M. A., Bashir, W., Koul, R., Raeburn, S., Gieselmann, V., Houlden, H., Crosby, A. H.
|
|
<strong>Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35).</strong>
|
|
Hum. Mutat. 31: E1251-1260, 2010. Note: Electronic Article.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20104589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20104589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20104589" 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.21205" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="3" class="mim-anchor"></a>
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<a id="Donkervoort2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Donkervoort, S., Dastgir, J., Hu, Y., Zein, W. M., Marks, H., Blackstone, C., Bonnemann, C. G.
|
|
<strong>Phenotypic variability of a likely FA2H founder mutation in a family with complicated hereditary spastic paraplegia. (Letter)</strong>
|
|
Clin. Genet. 85: 393-395, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23745665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23745665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23745665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.12185" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="4" class="mim-anchor"></a>
|
|
<a id="Eckhardt2005" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Eckhardt, M., Yaghootfam, A., Fewou, S. N., Zoller, I., Gieselmann, V.
|
|
<strong>A mammalian fatty acid hydroxylase responsible for the formation of alpha-hydroxylated galactosylceramide in myelin.</strong>
|
|
Biochem. J. 388: 245-254, 2005.
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|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15658937/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15658937</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15658937[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15658937" 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/10.1042/BJ20041451" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Edvardson2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Edvardson, S., Hama, H., Shaag, A., Gomori, J. M., Berger, I., Soffer, D., Korman, S. H., Taustein, I., Saada, A., Elpeleg, O.
|
|
<strong>Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.</strong>
|
|
Am. J. Hum. Genet. 83: 643-648, 2008.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19068277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19068277</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19068277[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19068277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2008.10.010" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Kruer2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kruer, M. C., Paisan-Ruiz, C., Boddaert, N., Yoon, M. Y., Hama, H., Gregory, A., Malandrini, A., Woltjer, R. L., Munnich, A., Gobin, S., Polster, B. J., Palmeri, S., Edvardson, S., Hardy, J., Houlden, H., Hayflick, S. J.
|
|
<strong>Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).</strong>
|
|
Ann. Neurol. 68: 611-618, 2010.
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|
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|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20853438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20853438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20853438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20853438" 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/ana.22122" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Pierson2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Pierson, T. M., Simeonov, D. R., Sincan, M., Adams, D. A., Markello, T., Golas, G., Fuentes-Fajardo, K., Hansen, N. F., Cherukuri, P. F., Cruz, P., Mullikin, J. C., Blackstone, C., Tifft, C., Boerkoel, C. F., Gahl, W. A.
|
|
<strong>Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration.</strong>
|
|
Europ. J. Hum. Genet. 20: 476-479, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22146942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22146942</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22146942[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22146942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2011.222" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Uchida2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Uchida, Y., Hama, H., Alderson, N. L., Douangpanya, S., Wang, Y., Crumrine, D. A., Elias, P. M., Holleran, W. M.
|
|
<strong>Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation.</strong>
|
|
J. Biol. Chem. 282: 13211-13219, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17355976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17355976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17355976" 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/10.1074/jbc.M611562200" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Zoller2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zoller, I., Meixner, M., Hartmann, D, Bussow, H., Meyer, R., Gieselmann, V., Eckhardt, M.
|
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<strong>Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration.</strong>
|
|
J. Neurosci. 28: 9741-9754, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18815260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18815260</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18815260[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18815260" 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/10.1523/JNEUROSCI.0458-08.2008" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 8/21/2014
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 5/29/2012<br>Cassandra L. Kniffin - updated : 2/17/2011<br>Cassandra L. Kniffin - updated : 11/26/2008
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Alan F. Scott : 5/15/2007
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/14/2024
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 11/24/2021<br>carol : 07/20/2020<br>mcolton : 05/08/2015<br>carol : 8/22/2014<br>ckniffin : 8/21/2014<br>carol : 9/20/2013<br>carol : 5/31/2012<br>ckniffin : 5/29/2012<br>wwang : 3/10/2011<br>ckniffin : 2/17/2011<br>carol : 1/20/2010<br>wwang : 12/5/2008<br>ckniffin : 11/26/2008<br>mgross : 5/15/2007
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 611026
|
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</span>
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</h3>
|
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
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FATTY ACID 2-HYDROXYLASE; FA2H
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-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>
|
|
<span class="mim-font">
|
|
FATTY ACID ALPHA-HYDROXYLASE; FAAH<br />
|
|
FATTY ACID HYDROXYLASE DOMAIN-CONTAINING PROTEIN 1; FAXDC1<br />
|
|
FAH1, S. CEREVISIAE, HOMOLOG OF; FAH1<br />
|
|
SCS7, S. CEREVISIAE, HOMOLOG OF; SCS7
|
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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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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: FA2H</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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|
<strong>SNOMEDCT:</strong> 764688002;
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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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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 16q23.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 16:74,712,969-74,774,820 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
16q23.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Spastic paraplegia 35, autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612319
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Sphingolipids are a large class of lipids found in all eukaryotic cells and are involved in numerous cellular processes. The structural diversity of sphingolipids stems from more than 300 distinct head groups, as well as from modifications of the hydrophobic ceramide moiety. FA2H catalyzes a common modification of the ceramide moiety: hydroxylation at the 2 position of the N-acyl chain. Sphingolipids containing 2-hydroxy fatty acid are common in nervous and epidermal tissue. Glycosphingolipids containing a high proportion of 2-hydroxy fatty acid are critical components of myelin, and several very long chain ceramides with 2-hydroxy fatty acids are important for the permeability barrier function of epidermis (summary by Alderson et al., 2004). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By searching databases for homologs of yeast Fah1, Alderson et al. (2004) identified human FA2H. The deduced 372-amino acid protein has a calculated molecular mass of 42.8 kD and shares 36% identity with yeast Fah1. FA2H contains an N-terminal cytochrome b5 (613218) domain, 4 transmembrane domains, and an iron-binding histidine motif conserved among membrane-bound desaturases and hydroxylases. Northern blot analysis showed highest expression of a 3-kb transcript in brain and colon, with lower levels in testis, prostate, pancreas, and kidney. FA2H was detected exclusively in the membrane fraction of transfected COS-7 cells. </p><p>Eckhardt et al. (2005) identified mouse Fa2h. Both mouse and human FA2H have a C-terminal endoplasmic reticulum (ER) retention motif, and immunofluorescence analysis showed that mouse Fa2h colocalized with calnexin (CANX; 114217), an ER marker protein, in transfected Chinese hamster ovary cells. Northern blot analysis detected Fa2h expression in mouse brain, stomach, skin, kidney, testis, and small intestine. In mouse brain, Fa2h expression increased strongly between 1 and 2 weeks of age, reached maximal level between 2 and 3 weeks of age, and decreased slightly in older animals. In situ hybridization of mouse brain showed highest expression in white matter. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kruer et al. (2010) stated that the FA2H gene maps to chromosome 16q23.1. </p><p>Eckhardt et al. (2005) mapped the mouse Fa2h gene to chromosome 8. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Alderson et al. (2004) found that COS-7 cells expressing human FA2H had 3- to 20-fold higher levels of 2-hydroxyceramides and 2-hydroxy fatty acids compared with control cells, and they observed a 40-fold increase in 2-hydroxyceramides in cells incubated 72 hrs. Deletion of the cytochrome b5 domain sharply reduced FA2H enzyme activity. </p><p>Using RT-PCR and Western blot analysis, Uchida et al. (2007) showed that FA2H was expressed in human keratinocytes and epidermis. FA2H expression and fatty acid 2-hydroxylase activity increased during differentiation. Downregulation of FA2H by small interfering RNA suppressed 2-hydroxylase activity and decreased levels of 2-hydroxyceramide and 2-hydroxyglucosylceramide in keratinocytes. Uchida et al. (2007) demonstrated that 2-hydroxylation of fatty acid by FA2H occurred before formation of ceramides and glucosylceramides, and that these lipids were required for formation of epidermal lamellar membranes. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In affected members of 2 unrelated consanguineous families with a complicated form of autosomal recessive spastic paraplegia (SPG35; 612319), Edvardson et al. (2008) identified a homozygous mutation in the FA2H gene (611026.0001). The patients had early onset of progressive spasticity, ataxia, dystonia, and cognitive decline associated with white matter abnormalities on brain MRI. Affected individuals from a third family with a less severe phenotype were found to have a different homozygous mutation in the FA2H gene (611026.0002). The relatively late onset of the disorders was consistent with the proposed need for FA2H at later stages of myelin maturation. </p><p>In affected members of an Omani family and a Pakistani family with complicated SPG35, Dick et al. (2010) identified 2 different homozygous mutations in the FA2H gene (611026.0003 and 611026.0004, respectively). The findings indicated that mutations in FA2H are associated with SPG35, and that abnormal hydroxylation of myelin galactocerebroside lipid components can lead to a severe progressive phenotype, with a clinical presentation of complicated SPG and radiological features of leukodystrophy. </p><p>Kruer et al. (2010) identified 2 different homozygous mutations in the FA2H gene (611026.0005 and 611026.0006) in affected members from 2 unrelated families with progressive complicated spastic paraplegia associated with brain iron deposition in the globus pallidus. The authors noted the connection between leukodystrophy and neurodegeneration with brain iron accumulation (NBIA). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Zoller et al. (2008) found that Fa2h-null mice lacked 2-hydroxylated sphingolipids in the brain and in peripheral nerves. However, nonhydroxylated galactosylceramide was increased, and oligodendrocyte differentiation, myelin formation, and peripheral nerve conduction velocities were normal up to 5 months of age. In contrast, aged 18-month-old Fa2h-null mice showed scattered axonal and myelin sheath degeneration in the spinal cord and more pronounced loss of myelin staining in sciatic nerves. These changes were associated with functional motor impairment. Zoller et al. (2008) concluded that the long-term maintenance of myelin is impaired in the absence of 2-hydroxylated sphingolipids and suggested that these lipids might be required for glial support of axon function. </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>8 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 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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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FA2H, IVS5DS, G-A, +1
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<br />
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SNP: rs1567633766,
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ClinVar: RCV000001098, RCV002512633
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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 7 affected members of 2 unrelated consanguineous Arab Muslim families with a complicated form of autosomal recessive spastic paraplegia (SPG35; 612319), Edvardson et al. (2008) identified a homozygous G-to-A transition in intron 5 of the FA2H gene, resulting in the skipping of exons 5 and 6 and predicted to abolish catalytic activity. The patients had early onset of progressive spasticity, ataxia, dystonia, and cognitive decline associated with white matter abnormalities on brain MRI. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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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FA2H, ASP35TYR
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<br />
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SNP: rs121918217,
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ClinVar: RCV000001099
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sisters, from a consanguineous Arab Muslim family, with a complicated form of spastic paraplegia (SPG35; 612319), Edvardson et al. (2008) identified a homozygous 103G-T transversion in exon 1 of the FA2H gene, resulting in an asp35-to-tyr (D35Y) substitution. The patients had mild spasticity and difficulty walking, but did not have cerebellar signs, dystonia, or impaired cognition. Both unaffected parents were heterozygous for the mutation. In vitro expression studies showed that the transfected D35Y-mutant had enzyme activity indistinguishable from an empty vector, suggesting that the D35Y mutation inactivated FA2H. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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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FA2H, ARG235CYS
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<br />
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SNP: rs387907039,
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gnomAD: rs387907039,
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ClinVar: RCV000023855, RCV001797590, RCV002509169
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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 affected members of a consanguineous Omani family with complicated autosomal recessive spastic paraplegia-35 (SPG35; 612319), Dick et al. (2010) identified a homozygous 703C-T transition in exon 5 of the FA2H gene, resulting in an arg235-to-cys (R235C) substitution. The mutation was not found in 700 control chromosomes. In vitro functional expression studies showed that the mutation resulted in a reduction in hydroxylated ceramides to 60-80% of wildtype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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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FA2H, 18-BP DEL
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<br />
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SNP: rs759947457,
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gnomAD: rs759947457,
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ClinVar: RCV000023856, RCV002293414, RCV002513206
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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>In affected members of a consanguineous Pakistani family with complicated autosomal recessive spastic paraplegia-35 (SPG35; 612319), Dick et al. (2010) identified a homozygous 18-bp deletion in exon 1 of the FA2H gene, resulting in the loss of 6 amino acids (53-58) in the cytochrome B5 domain of the protein. The mutation was not found in 200 control chromosomes. In vitro functional expression studies showed that the mutation resulted in undetectable levels of hydroxylated ceramides. </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>.0005 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE</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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FA2H, ARG154CYS
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<br />
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SNP: rs387907040,
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gnomAD: rs387907040,
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ClinVar: RCV000023857, RCV000483483, RCV002513207, RCV003317044
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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>In 3 Italian brothers, born of consanguineous parents, with a complicated form of autosomal recessive spastic paraplegia-35 (SPG35; 612319) and evidence of brain iron accumulation in the globus pallidus, Kruer et al. (2010) identified a homozygous 460C-T transition in exon 3 of the FA2H gene, resulting in an arg154-to-cys (R154C) substitution in a highly conserved residue. Western blot analysis of COS-7 cells transfected with the R154C mutation showed decreased FA2H protein levels. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0006 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE, WITH OR WITHOUT NEURODEGENERATION</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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FA2H, 2-BP DEL, 509AC
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<br />
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SNP: rs587776891,
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ClinVar: RCV000023858, RCV002513208, RCV004700275
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In 2 Albanian brothers with a complicated form of autosomal recessive spastic paraplegia-35 (SPG35; 612319) and evidence of brain iron accumulation in the globus pallidus, Kruer et al. (2010) identified a homozygous 2-bp deletion (c.509_510delAC) in the FA2H gene, resulting in a frameshift and premature termination. </p><p>Donkervoort et al. (2014) identified homozygosity for the c.509_510delAC deletion in the FA2H gene, which resulted in a frameshift and a premature stop codon (Tyr170Ter), in a brother and sister from Montenegro with SPG35. The mutation segregated with the disorder in the family; functional studies were not performed. Both children had typical features of the disorder, but no brain iron accumulation was seen on brain MRI. Because this mutation had been identified by Kruer et al. (2010) in 2 brothers from Albania with a similar neurodegenerative disorder with brain iron accumulation, Donkervoort et al. (2014) suggested that it may represent a founder mutation in individuals from the Balkan region. </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>.0007 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE, WITH NEURODEGENERATION</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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FA2H, PHE236SER
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<br />
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SNP: rs387907172,
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ClinVar: RCV000024321
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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 10-year-old boy, born of unrelated parents, with a complicated form of autosomal recessive spastic paraplegia-35 (SPG35; 612319), Pierson et al. (2012) identified compound heterozygosity for a heterozygous 707T-C transition in exon 5 of the FA2H gene, resulting in a phe236-to-ser (F236S) substitution inherited from the unaffected father, and a 28-kb deletion encompassing exons 3 to 7 of the FA2H gene (611026.0008) inherited from the unaffected mother. The F236S substitution occurred in a highly conserved residue in an iron-binding histidine motif in the catalytic site. The patient developed normally until age 3 years, when he developed progressive neurodegeneration following a febrile illness. He had lower extremity weakness and atrophy, spasticity, dystonic foot inversion, and poor balance. He also had dysarthria, neck weakness, mask-like facies, hunched posture, and mild cognitive deficits, but did not have optic atrophy or seizures. Serial brain MRIs showed progressive neurodegenerative changes, with white matter abnormalities, cerebellar and brainstem atrophy, thin corpus callosum, and evidence of demyelination. He also had an axonal sensory neuropathy. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0008 SPASTIC PARAPLEGIA 35, AUTOSOMAL RECESSIVE, WITH NEURODEGENERATION</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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FA2H, 28-KB DEL
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<br />
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ClinVar: RCV000024322
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>For discussion of the 28-kb deletion in the FA2H gene that was found in compound heterozygous state in a patient with autosomal recessive spastic paraplegia-35 (SPG35; 612319) by Pierson et al. (2012), see 611026.0007. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
|
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<li>
|
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<p class="mim-text-font">
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Alderson, N. L., Rembiesa, B. M., Walla, M. D., Bielawska, A., Bielawski, J., Hama, H.
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<strong>The human FA2H gene encodes a fatty acid 2-hydroxylase.</strong>
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J. Biol. Chem. 279: 48562-48568, 2004.
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[PubMed: 15337768]
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[Full Text: https://doi.org/10.1074/jbc.M406649200]
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Dick, K. J., Eckhardt, M., Paisan-Ruiz, C., Alshehhi, A. A., Proukakis, C., Sibtain, N. A., Maier, H., Sharifi, R., Patton, M. A., Bashir, W., Koul, R., Raeburn, S., Gieselmann, V., Houlden, H., Crosby, A. H.
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<strong>Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35).</strong>
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Hum. Mutat. 31: E1251-1260, 2010. Note: Electronic Article.
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[PubMed: 20104589]
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[Full Text: https://doi.org/10.1002/humu.21205]
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Donkervoort, S., Dastgir, J., Hu, Y., Zein, W. M., Marks, H., Blackstone, C., Bonnemann, C. G.
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<strong>Phenotypic variability of a likely FA2H founder mutation in a family with complicated hereditary spastic paraplegia. (Letter)</strong>
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Clin. Genet. 85: 393-395, 2014.
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[PubMed: 23745665]
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[Full Text: https://doi.org/10.1111/cge.12185]
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Eckhardt, M., Yaghootfam, A., Fewou, S. N., Zoller, I., Gieselmann, V.
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<strong>A mammalian fatty acid hydroxylase responsible for the formation of alpha-hydroxylated galactosylceramide in myelin.</strong>
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Biochem. J. 388: 245-254, 2005.
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[PubMed: 15658937]
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[Full Text: https://doi.org/10.1042/BJ20041451]
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Edvardson, S., Hama, H., Shaag, A., Gomori, J. M., Berger, I., Soffer, D., Korman, S. H., Taustein, I., Saada, A., Elpeleg, O.
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<strong>Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.</strong>
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Am. J. Hum. Genet. 83: 643-648, 2008.
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[PubMed: 19068277]
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[Full Text: https://doi.org/10.1016/j.ajhg.2008.10.010]
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Kruer, M. C., Paisan-Ruiz, C., Boddaert, N., Yoon, M. Y., Hama, H., Gregory, A., Malandrini, A., Woltjer, R. L., Munnich, A., Gobin, S., Polster, B. J., Palmeri, S., Edvardson, S., Hardy, J., Houlden, H., Hayflick, S. J.
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<strong>Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).</strong>
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Ann. Neurol. 68: 611-618, 2010.
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[PubMed: 20853438]
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[Full Text: https://doi.org/10.1002/ana.22122]
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Pierson, T. M., Simeonov, D. R., Sincan, M., Adams, D. A., Markello, T., Golas, G., Fuentes-Fajardo, K., Hansen, N. F., Cherukuri, P. F., Cruz, P., Mullikin, J. C., Blackstone, C., Tifft, C., Boerkoel, C. F., Gahl, W. A.
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<strong>Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration.</strong>
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Europ. J. Hum. Genet. 20: 476-479, 2012.
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[PubMed: 22146942]
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[Full Text: https://doi.org/10.1038/ejhg.2011.222]
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Uchida, Y., Hama, H., Alderson, N. L., Douangpanya, S., Wang, Y., Crumrine, D. A., Elias, P. M., Holleran, W. M.
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<strong>Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation.</strong>
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J. Biol. Chem. 282: 13211-13219, 2007.
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[PubMed: 17355976]
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[Full Text: https://doi.org/10.1074/jbc.M611562200]
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Zoller, I., Meixner, M., Hartmann, D, Bussow, H., Meyer, R., Gieselmann, V., Eckhardt, M.
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<strong>Absence of 2-hydroxylated sphingolipids is compatible with normal neural development but causes late-onset axon and myelin sheath degeneration.</strong>
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J. Neurosci. 28: 9741-9754, 2008.
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[PubMed: 18815260]
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[Full Text: https://doi.org/10.1523/JNEUROSCI.0458-08.2008]
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Cassandra L. Kniffin - updated : 8/21/2014<br>Cassandra L. Kniffin - updated : 5/29/2012<br>Cassandra L. Kniffin - updated : 2/17/2011<br>Cassandra L. Kniffin - updated : 11/26/2008
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