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Entry
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- *612035 - ALANYL-tRNA SYNTHETASE 2; AARS2
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- OMIM
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<p>
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<span class="h4">*612035</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/612035">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div 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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<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=ENSG00000124608;t=ENST00000244571" 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=57505" 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=612035" 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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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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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=ENSG00000124608;t=ENST00000244571" 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_020745,XM_005249245,XR_007059282" 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_020745" 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=612035" 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=12397&isoform_id=12397_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/AARS2" 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/15488935,21619898,74742244,119624673,124297995,124504241,530382281,929654477,1519312576,2462609777" 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/Q5JTZ9" 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 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=57505" 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=ENSG00000124608;t=ENST00000244571" 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=AARS2" 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=AARS2" 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+57505" 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/AARS2" 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:57505" 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/57505" 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=chr6&hgg_gene=ENST00000244571.5&hgg_start=44298731&hgg_end=44313347&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 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:21022" 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:21022" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=612035[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=612035[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/AARS2/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/ENSG00000124608" 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=AARS2" 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=AARS2" 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=AARS2" 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=AARS2&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/PA162375129" 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:21022" 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/FBgn0028962.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:2681839" 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/AARS2#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:2681839" 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/57505/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=57505" 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=WBGene00000196;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-041008-213" 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://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:57505" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=AARS2&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> 733600007<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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612035
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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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ALANYL-tRNA SYNTHETASE 2; AARS2
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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>
|
|
<span class="mim-font">
|
|
ALANYL-tRNA SYNTHETASE, MITOCHONDRIAL<br />
|
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MT-ALARS<br />
|
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KIAA1270
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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=AARS2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">AARS2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/6/545?start=-3&limit=10&highlight=545">6p21.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:44298731-44313347&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'})">6:44,298,731-44,313,347</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=614096,615889" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
|
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
|
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<tr>
|
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<td rowspan="2">
|
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<span class="mim-font">
|
|
<a href="/geneMap/6/545?start=-3&limit=10&highlight=545">
|
|
6p21.1
|
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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">
|
|
Combined oxidative phosphorylation deficiency 8
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/614096"> 614096 </a>
|
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Leukoencephalopathy, progressive, with ovarian failure
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/615889"> 615889 </a>
|
|
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<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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<p>The AARS2 gene encodes mitochondrial alanyl-tRNA synthetase, which is responsible for the charging of tRNA-ala with alanine during mitochondrial translation (summary by <a href="#3" class="mim-tip-reference" title="Gotz, A., Tyynismaa, H., Euro, L., Ellonen, P., Hyotylainen, T., Ojala, T., Hamalainen, R. H., Tommiska, J., Raivio, T., Oresic, M., Karikoski, R., Tammela, O., Simola, K. O., Paetau, A., Tyni, T., Suomalainen, A. <strong>Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy.</strong> Am. J. Hum. Genet. 88: 635-642, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549344[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.2011.04.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549344">Gotz et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, <a href="#4" class="mim-tip-reference" title="Nagase, T., Ishikawa, K., Kikuno, R., Hirosawa, M., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 6: 337-345, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10574462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10574462</a>] [<a href="https://doi.org/10.1093/dnares/6.5.337" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10574462">Nagase et al. (1999)</a> cloned AARS2, which they designated KIAA1270. The mRNA contains repetitive elements in its 3-prime end, and the deduced 986-amino acid protein shares 46% identity with human AARS (<a href="/entry/601065">601065</a>). RT-PCR ELISA showed moderate to high expression of AARS2 in all adult and fetal tissues examined, with highest expression in ovary. Expression was high in all adult brain regions examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10574462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By searching a database for tRNA synthetases, <a href="#1" class="mim-tip-reference" title="Bonnefond, L., Fender, A., Rudinger-Thirion, J., Giege, R., Florentz, C., Sissler, M. <strong>Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS.</strong> Biochemistry 44: 4805-4816, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15779907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15779907</a>] [<a href="https://doi.org/10.1021/bi047527z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15779907">Bonnefond et al. (2005)</a> identified AARS2, which they called MT-ALARS. The deduced 985-amino acid protein has a 68-amino acid mitochondrial targeting signal, resulting in a mature protein of 917 amino acids. AARS2 is a class II amino acid tRNA synthetase, with a C-terminal active-site domain linked to an N-terminal anticodon-binding domain by a short hinge. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15779907" 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="Bonnefond, L., Fender, A., Rudinger-Thirion, J., Giege, R., Florentz, C., Sissler, M. <strong>Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS.</strong> Biochemistry 44: 4805-4816, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15779907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15779907</a>] [<a href="https://doi.org/10.1021/bi047527z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15779907">Bonnefond et al. (2005)</a> determined that the AARS2 gene contains 22 exons and spans 13.7 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15779907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By radiation hybrid analysis, <a href="#4" class="mim-tip-reference" title="Nagase, T., Ishikawa, K., Kikuno, R., Hirosawa, M., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong> DNA Res. 6: 337-345, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10574462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10574462</a>] [<a href="https://doi.org/10.1093/dnares/6.5.337" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10574462">Nagase et al. (1999)</a> mapped the AARS2 gene to chromosome 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10574462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Combined Oxidative Phosphorylation Deficiency 8</em></strong></p><p>
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By exome sequencing, <a href="#3" class="mim-tip-reference" title="Gotz, A., Tyynismaa, H., Euro, L., Ellonen, P., Hyotylainen, T., Ojala, T., Hamalainen, R. H., Tommiska, J., Raivio, T., Oresic, M., Karikoski, R., Tammela, O., Simola, K. O., Paetau, A., Tyni, T., Suomalainen, A. <strong>Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy.</strong> Am. J. Hum. Genet. 88: 635-642, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549344[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.2011.04.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549344">Gotz et al. (2011)</a> identified a homozygous mutation in the AARS2 gene (R592W; <a href="#0001">612035.0001</a>) in a Finnish girl with combined oxidative phosphorylation deficiency-8 (COXPD8; <a href="/entry/614096">614096</a>) manifest as fatal infantile hypertrophic mitochondrial cardiomyopathy and death at age 10 months. An second unrelated Finnish female infant with a more severe mitochondrial cardiomyopathy resulting in death at age 3 days was found to be compound heterozygous for the R592W mutation and a second mutation (<a href="#0002">612035.0002</a>). The mutations affected the editing and catalytic aminoacylation domains, respectively. Both patients had near-total deficiency of respiratory complexes I, III, and IV in heart tissue, with less severe defects in brain and skeletal muscle; the liver was not affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549344" 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 5 unrelated patients of European descent with COXPD8 manifest as fatal infantile cardiomyopathy, <a href="#5" class="mim-tip-reference" title="Taylor, R. W., Pyle, A., Griffin, H., Blakely, E. L., Duff, J., He, L., Smertenko, T., Alston, C. L., Neeve, V. C., Best, A., Yarham, J. W., Kirschner, J., and 17 others. <strong>Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.</strong> JAMA 312: 68-77, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25058219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25058219</a>] [<a href="https://doi.org/10.1001/jama.2014.7184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25058219">Taylor et al. (2014)</a> identified homozygous or compound heterozygous mutations in the AARS2 gene (see, e.g., <a href="#0001">612035.0001</a> and <a href="#0003">612035.0003</a>). All of the patients carried the R592W mutation on at least 1 allele, and haplotype analysis indicated a founder effect for this mutation. Functional studies of the variants were not performed. The patients were part of a study of 53 patients with mitochondrial respiratory chain complex deficiencies who underwent whole-exome sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25058219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Progressive Leukoencephalopathy With Ovarian Failure</em></strong></p><p>
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In 6 patients with progressive leukoencephalopathy (LKENP; <a href="/entry/615889">615889</a>), including 5 women with premature ovarian failure, <a href="#2" class="mim-tip-reference" title="Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others. <strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong> Neurology 82: 2063-2071, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808023</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808023[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/10.1212/WNL.0000000000000497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24808023">Dallabona et al. (2014)</a> identified compound heterozygous mutations in the AARS2 gene (see, e.g., <a href="#0004">612035.0004</a>-<a href="#0007">612035.0007</a>). The mutations in the first 2 patients were found by whole-exome sequencing. Direct sequencing of the AARS2 gene identified pathogenic biallelic mutations in 4 of 11 additional patients with leukodystrophy. The patients had a severe neurodegenerative disorder characterized by loss of motor and cognitive skills, with onset in young adulthood. Studies of the yeast homologs of 2 variants (F50C, <a href="#0004">612035.0004</a> and R521X, <a href="#0005">612035.0005</a>) showed that they resulted in a complete or partial loss of protein function; functional studies of the other variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24808023" 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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AARS2, ARG592TRP (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs138119149;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs138119149</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs138119149 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs138119149;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/rs138119149?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=rs138119149" 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=rs138119149" 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=RCV000023929 OR RCV000196012 OR RCV000622422 OR RCV000754863 OR RCV004760340" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023929, RCV000196012, RCV000622422, RCV000754863, RCV004760340" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023929...</a>
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<p>In a Finnish girl with combined oxidative phosphorylation deficiency-8 (COXPD8; <a href="/entry/614096">614096</a>) manifest as fatal infantile hypertrophic mitochondrial cardiomyopathy, <a href="#3" class="mim-tip-reference" title="Gotz, A., Tyynismaa, H., Euro, L., Ellonen, P., Hyotylainen, T., Ojala, T., Hamalainen, R. H., Tommiska, J., Raivio, T., Oresic, M., Karikoski, R., Tammela, O., Simola, K. O., Paetau, A., Tyni, T., Suomalainen, A. <strong>Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy.</strong> Am. J. Hum. Genet. 88: 635-642, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549344[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.2011.04.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549344">Gotz et al. (2011)</a> identified a homozygous 1774C-T transition in exon 13 of the AARS2 gene, resulting in an arg592-to-trp (R592W) substitution predicted to impair the editing domain, causing mistranslation. This patient died at age 10 months. Each unaffected parent was heterozygous for the mutation. An unrelated Finnish female infant with the disorder was found to be compound heterozygous for the R592W mutation and a 464T-G transversion in exon 3, resulting in a leu155-to-arg (L155R; <a href="#0002">612035.0002</a>) substitution affecting the catalytic aminoacylation domain and causing lack of tRNA aminoacylation. She died on day 3 of life. Her parents were heterozygous carriers of the respective mutations. Both mutations affected highly conserved residues and were not found in 400 Finnish control chromosomes. The mutations caused a near-total deficiency of respiratory chain complexes I, III, and IV in the hearts of the patients, resulting in the primary manifestation of hypertrophic cardiomyopathy, although the brain and skeletal muscles also showed milder respiratory chain defects, suggesting a multisystem disorder. The liver was not affected in either patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Taylor, R. W., Pyle, A., Griffin, H., Blakely, E. L., Duff, J., He, L., Smertenko, T., Alston, C. L., Neeve, V. C., Best, A., Yarham, J. W., Kirschner, J., and 17 others. <strong>Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.</strong> JAMA 312: 68-77, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25058219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25058219</a>] [<a href="https://doi.org/10.1001/jama.2014.7184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25058219">Taylor et al. (2014)</a> identified the R592W mutation (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs138119149;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs138119149</a>) in 5 unrelated patients of European origin with COXPD8 manifest as fatal infantile cardiomyopathy. Two patients were homozygous for the mutation, whereas 3 were compound heterozygous for R592W and another pathogenic mutation (see, e.g., <a href="#0003">612035.0003</a>). The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. R592W was not found in the 1000 Genomes Project database or in 238 in-house controls, but it was present at very low frequency (0.0002) in the Exome Sequencing Project database. Haplotype analysis indicated a founder effect for R592W. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25058219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387907061 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907061;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/rs387907061?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=rs387907061" 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=rs387907061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the leu155-to-arg (L155R) mutation in the AARS2 gene that was found in compound heterozygous state in a patient with combined oxidative phosphorylation deficiency-8 (COXPD8; <a href="/entry/614096">614096</a>) by <a href="#3" class="mim-tip-reference" title="Gotz, A., Tyynismaa, H., Euro, L., Ellonen, P., Hyotylainen, T., Ojala, T., Hamalainen, R. H., Tommiska, J., Raivio, T., Oresic, M., Karikoski, R., Tammela, O., Simola, K. O., Paetau, A., Tyni, T., Suomalainen, A. <strong>Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy.</strong> Am. J. Hum. Genet. 88: 635-642, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549344[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.2011.04.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21549344">Gotz et al. (2011)</a>, see <a href="#0001">612035.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21549344" 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 yeast studies, <a href="#2" class="mim-tip-reference" title="Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others. <strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong> Neurology 82: 2063-2071, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808023</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808023[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/10.1212/WNL.0000000000000497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24808023">Dallabona et al. (2014)</a> found that the L155R mutation behaved as a null allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24808023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777589 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777589;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=rs587777589" 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=rs587777589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a British girl with combined oxidative phosphorylation deficiency-8 (COXPD8; <a href="/entry/614096">614096</a>) manifest as fatal infantile cardiomyopathy, <a href="#5" class="mim-tip-reference" title="Taylor, R. W., Pyle, A., Griffin, H., Blakely, E. L., Duff, J., He, L., Smertenko, T., Alston, C. L., Neeve, V. C., Best, A., Yarham, J. W., Kirschner, J., and 17 others. <strong>Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.</strong> JAMA 312: 68-77, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25058219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25058219</a>] [<a href="https://doi.org/10.1001/jama.2014.7184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25058219">Taylor et al. (2014)</a> identified compound heterozygosity for 2 mutations in the AARS2 gene: a 1-bp insertion (c.647_648insG), resulting in a frameshift and premature termination (Cys218LeufsTer6), and R592W (<a href="#0001">612035.0001</a>). She died at 3 months of age. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. The c.647insG mutation was not present in the Exome Sequencing Project, 1000 Genomes Project, or dbSNP (build 137) databases or in 238 in-house controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25058219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777590 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777590;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=rs587777590" 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=rs587777590" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a young woman with progressive leukoencephalopathy with ovarian failure (LKENP; <a href="/entry/615889">615889</a>), <a href="#2" class="mim-tip-reference" title="Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others. <strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong> Neurology 82: 2063-2071, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808023</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808023[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/10.1212/WNL.0000000000000497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24808023">Dallabona et al. (2014)</a> identified compound heterozygous mutations in the AARS2 gene: a c.149T-G transversion in exon 1, resulting in a phe50-to-cys (F50C) substitution at a highly conserved residue in the aminoacylation domain, and a c.1561C-T transition in exon 11, resulting in an arg521-to-ter (R521X; <a href="#0005">612035.0005</a>) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and were present at a frequency of less than 0.01% in the Exome Variant Server database. Studies in the yeast ala1 homolog indicated that the truncating mutant failed to restore growth in a functionally incompetent strain, consistent with a loss of function. The missense mutation was similar to wildtype at 28 degrees C, but it resulted in reduced growth at 37 degree C. The findings suggested that the F50C mutation is deleterious only under stress conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24808023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587777591 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777591;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/rs587777591?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=rs587777591" 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=rs587777591" 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=RCV000132554 OR RCV000578231 OR RCV001781479" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000132554, RCV000578231, RCV001781479" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000132554...</a>
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<p>For discussion of the arg521-to-ter (R521X) in the AARS2 gene that was found in compound heterozygous state in a patient with progressive leukoencephalopathy with ovarian failure (LKENP; <a href="/entry/615889">615889</a>) by <a href="#2" class="mim-tip-reference" title="Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others. <strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong> Neurology 82: 2063-2071, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808023</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808023[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/10.1212/WNL.0000000000000497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24808023">Dallabona et al. (2014)</a>, see <a href="#0004">612035.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24808023" 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 LEUKOENCEPHALOPATHY, PROGRESSIVE, WITH OVARIAN FAILURE</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> rs543267101 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs543267101;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/rs543267101?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=rs543267101" 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=rs543267101" 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=RCV000132555 OR RCV001753519" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000132555, RCV001753519" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000132555...</a>
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<p>In a man with progressive leukoencephalopathy (LKENP; <a href="/entry/615889">615889</a>), <a href="#2" class="mim-tip-reference" title="Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others. <strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong> Neurology 82: 2063-2071, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808023</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808023[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/10.1212/WNL.0000000000000497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24808023">Dallabona et al. (2014)</a> identified compound heterozygous mutations in the AARS2 gene: a c.2893G-A transition, resulting in a gly965-to-arg (G965R) substitution, and a c.1213G-A transition, resulting in a glu405-to-lys (E405K; <a href="#0007">612035.0007</a>) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and were present at a frequency of less than 0.01% in the Exome Variant Server database. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24808023" 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 LEUKOENCEPHALOPATHY, PROGRESSIVE, WITH OVARIAN FAILURE</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> rs587777592 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777592;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/rs587777592?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=rs587777592" 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=rs587777592" 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=RCV000132556 OR RCV001844048" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000132556, RCV001844048" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000132556...</a>
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<p>For discussion of the glu405-to-lys (E405K) mutation in the AARS2 gene that was found in compound heterozygous state in a patient with progressive leukoencephalopathy (LKENP; <a href="/entry/615889">615889</a>) by <a href="#2" class="mim-tip-reference" title="Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others. <strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong> Neurology 82: 2063-2071, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808023</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808023[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/10.1212/WNL.0000000000000497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24808023">Dallabona et al. (2014)</a>, see <a href="#0006">612035.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24808023" 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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Bonnefond, L., Fender, A., Rudinger-Thirion, J., Giege, R., Florentz, C., Sissler, M.
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<strong>Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS.</strong>
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Biochemistry 44: 4805-4816, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15779907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15779907</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15779907" 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/10.1021/bi047527z" target="_blank">Full Text</a>]
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Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others.
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<strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong>
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Neurology 82: 2063-2071, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808023</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808023[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=24808023" 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/10.1212/WNL.0000000000000497" target="_blank">Full Text</a>]
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Gotz, A., Tyynismaa, H., Euro, L., Ellonen, P., Hyotylainen, T., Ojala, T., Hamalainen, R. H., Tommiska, J., Raivio, T., Oresic, M., Karikoski, R., Tammela, O., Simola, K. O., Paetau, A., Tyni, T., Suomalainen, A.
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<strong>Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy.</strong>
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Am. J. Hum. Genet. 88: 635-642, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21549344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21549344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21549344[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=21549344" 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.2011.04.006" target="_blank">Full Text</a>]
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Nagase, T., Ishikawa, K., Kikuno, R., Hirosawa, M., Nomura, N., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
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DNA Res. 6: 337-345, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10574462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10574462</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10574462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/dnares/6.5.337" target="_blank">Full Text</a>]
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Taylor, R. W., Pyle, A., Griffin, H., Blakely, E. L., Duff, J., He, L., Smertenko, T., Alston, C. L., Neeve, V. C., Best, A., Yarham, J. W., Kirschner, J., and 17 others.
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<strong>Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.</strong>
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JAMA 312: 68-77, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25058219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25058219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25058219" 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/10.1001/jama.2014.7184" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 7/31/2014
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Cassandra L. Kniffin - updated : 7/19/2011
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<span class="mim-text-font">
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mcolton : 07/01/2015
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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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alopez : 8/4/2014<br>mcolton : 7/31/2014<br>ckniffin : 7/31/2014<br>wwang : 7/21/2011<br>ckniffin : 7/19/2011<br>mgross : 5/8/2008
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</span>
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</div>
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<div class="container visible-print-block">
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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">
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<strong>*</strong> 612035
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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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ALANYL-tRNA SYNTHETASE 2; AARS2
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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>
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<span class="mim-font">
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ALANYL-tRNA SYNTHETASE, MITOCHONDRIAL<br />
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MT-ALARS<br />
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KIAA1270
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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: AARS2</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> 733600007;
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</span>
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</p>
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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>
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Cytogenetic location: 6p21.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:44,298,731-44,313,347 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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6p21.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Combined oxidative phosphorylation deficiency 8
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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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614096
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Leukoencephalopathy, progressive, with ovarian failure
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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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615889
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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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>The AARS2 gene encodes mitochondrial alanyl-tRNA synthetase, which is responsible for the charging of tRNA-ala with alanine during mitochondrial translation (summary by Gotz et al., 2011). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (1999) cloned AARS2, which they designated KIAA1270. The mRNA contains repetitive elements in its 3-prime end, and the deduced 986-amino acid protein shares 46% identity with human AARS (601065). RT-PCR ELISA showed moderate to high expression of AARS2 in all adult and fetal tissues examined, with highest expression in ovary. Expression was high in all adult brain regions examined. </p><p>By searching a database for tRNA synthetases, Bonnefond et al. (2005) identified AARS2, which they called MT-ALARS. The deduced 985-amino acid protein has a 68-amino acid mitochondrial targeting signal, resulting in a mature protein of 917 amino acids. AARS2 is a class II amino acid tRNA synthetase, with a C-terminal active-site domain linked to an N-terminal anticodon-binding domain by a short hinge. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bonnefond et al. (2005) determined that the AARS2 gene contains 22 exons and spans 13.7 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>By radiation hybrid analysis, Nagase et al. (1999) mapped the AARS2 gene to chromosome 6. </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><strong><em>Combined Oxidative Phosphorylation Deficiency 8</em></strong></p><p>
|
|
By exome sequencing, Gotz et al. (2011) identified a homozygous mutation in the AARS2 gene (R592W; 612035.0001) in a Finnish girl with combined oxidative phosphorylation deficiency-8 (COXPD8; 614096) manifest as fatal infantile hypertrophic mitochondrial cardiomyopathy and death at age 10 months. An second unrelated Finnish female infant with a more severe mitochondrial cardiomyopathy resulting in death at age 3 days was found to be compound heterozygous for the R592W mutation and a second mutation (612035.0002). The mutations affected the editing and catalytic aminoacylation domains, respectively. Both patients had near-total deficiency of respiratory complexes I, III, and IV in heart tissue, with less severe defects in brain and skeletal muscle; the liver was not affected. </p><p>In 5 unrelated patients of European descent with COXPD8 manifest as fatal infantile cardiomyopathy, Taylor et al. (2014) identified homozygous or compound heterozygous mutations in the AARS2 gene (see, e.g., 612035.0001 and 612035.0003). All of the patients carried the R592W mutation on at least 1 allele, and haplotype analysis indicated a founder effect for this mutation. Functional studies of the variants were not performed. The patients were part of a study of 53 patients with mitochondrial respiratory chain complex deficiencies who underwent whole-exome sequencing. </p><p><strong><em>Progressive Leukoencephalopathy With Ovarian Failure</em></strong></p><p>
|
|
In 6 patients with progressive leukoencephalopathy (LKENP; 615889), including 5 women with premature ovarian failure, Dallabona et al. (2014) identified compound heterozygous mutations in the AARS2 gene (see, e.g., 612035.0004-612035.0007). The mutations in the first 2 patients were found by whole-exome sequencing. Direct sequencing of the AARS2 gene identified pathogenic biallelic mutations in 4 of 11 additional patients with leukodystrophy. The patients had a severe neurodegenerative disorder characterized by loss of motor and cognitive skills, with onset in young adulthood. Studies of the yeast homologs of 2 variants (F50C, 612035.0004 and R521X, 612035.0005) showed that they resulted in a complete or partial loss of protein function; functional studies of the other variants were not performed. </p>
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</span>
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>7 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 8</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
AARS2, ARG592TRP ({dbSNP rs138119149})
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs138119149,
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|
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gnomAD: rs138119149,
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|
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ClinVar: RCV000023929, RCV000196012, RCV000622422, RCV000754863, RCV004760340
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Finnish girl with combined oxidative phosphorylation deficiency-8 (COXPD8; 614096) manifest as fatal infantile hypertrophic mitochondrial cardiomyopathy, Gotz et al. (2011) identified a homozygous 1774C-T transition in exon 13 of the AARS2 gene, resulting in an arg592-to-trp (R592W) substitution predicted to impair the editing domain, causing mistranslation. This patient died at age 10 months. Each unaffected parent was heterozygous for the mutation. An unrelated Finnish female infant with the disorder was found to be compound heterozygous for the R592W mutation and a 464T-G transversion in exon 3, resulting in a leu155-to-arg (L155R; 612035.0002) substitution affecting the catalytic aminoacylation domain and causing lack of tRNA aminoacylation. She died on day 3 of life. Her parents were heterozygous carriers of the respective mutations. Both mutations affected highly conserved residues and were not found in 400 Finnish control chromosomes. The mutations caused a near-total deficiency of respiratory chain complexes I, III, and IV in the hearts of the patients, resulting in the primary manifestation of hypertrophic cardiomyopathy, although the brain and skeletal muscles also showed milder respiratory chain defects, suggesting a multisystem disorder. The liver was not affected in either patient. </p><p>Taylor et al. (2014) identified the R592W mutation (rs138119149) in 5 unrelated patients of European origin with COXPD8 manifest as fatal infantile cardiomyopathy. Two patients were homozygous for the mutation, whereas 3 were compound heterozygous for R592W and another pathogenic mutation (see, e.g., 612035.0003). The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. R592W was not found in the 1000 Genomes Project database or in 238 in-house controls, but it was present at very low frequency (0.0002) in the Exome Sequencing Project database. Haplotype analysis indicated a founder effect for R592W. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 8</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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AARS2, LEU155ARG
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<br />
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SNP: rs387907061,
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gnomAD: rs387907061,
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ClinVar: RCV000023930
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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 leu155-to-arg (L155R) mutation in the AARS2 gene that was found in compound heterozygous state in a patient with combined oxidative phosphorylation deficiency-8 (COXPD8; 614096) by Gotz et al. (2011), see 612035.0001. </p><p>In yeast studies, Dallabona et al. (2014) found that the L155R mutation behaved as a null allele. </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 COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 8</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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AARS2, 1-BP INS, 647G
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<br />
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SNP: rs587777589,
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ClinVar: RCV000132552, RCV000754864, RCV000790768
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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 a British girl with combined oxidative phosphorylation deficiency-8 (COXPD8; 614096) manifest as fatal infantile cardiomyopathy, Taylor et al. (2014) identified compound heterozygosity for 2 mutations in the AARS2 gene: a 1-bp insertion (c.647_648insG), resulting in a frameshift and premature termination (Cys218LeufsTer6), and R592W (612035.0001). She died at 3 months of age. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. The c.647insG mutation was not present in the Exome Sequencing Project, 1000 Genomes Project, or dbSNP (build 137) databases or in 238 in-house controls. </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 LEUKOENCEPHALOPATHY, PROGRESSIVE, WITH OVARIAN FAILURE</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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AARS2, PHE50CYS
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<br />
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SNP: rs587777590,
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ClinVar: RCV000132553
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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 young woman with progressive leukoencephalopathy with ovarian failure (LKENP; 615889), Dallabona et al. (2014) identified compound heterozygous mutations in the AARS2 gene: a c.149T-G transversion in exon 1, resulting in a phe50-to-cys (F50C) substitution at a highly conserved residue in the aminoacylation domain, and a c.1561C-T transition in exon 11, resulting in an arg521-to-ter (R521X; 612035.0005) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and were present at a frequency of less than 0.01% in the Exome Variant Server database. Studies in the yeast ala1 homolog indicated that the truncating mutant failed to restore growth in a functionally incompetent strain, consistent with a loss of function. The missense mutation was similar to wildtype at 28 degrees C, but it resulted in reduced growth at 37 degree C. The findings suggested that the F50C mutation is deleterious only under stress conditions. </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>.0005 LEUKOENCEPHALOPATHY, PROGRESSIVE, WITH OVARIAN FAILURE</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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AARS2, ARG521TER
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<br />
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SNP: rs587777591,
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gnomAD: rs587777591,
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ClinVar: RCV000132554, RCV000578231, RCV001781479
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</span>
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</div>
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<span class="mim-text-font">
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<p>For discussion of the arg521-to-ter (R521X) in the AARS2 gene that was found in compound heterozygous state in a patient with progressive leukoencephalopathy with ovarian failure (LKENP; 615889) by Dallabona et al. (2014), see 612035.0004. </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 LEUKOENCEPHALOPATHY, PROGRESSIVE, WITH OVARIAN FAILURE</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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AARS2, GLY965ARG
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<br />
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SNP: rs543267101,
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gnomAD: rs543267101,
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ClinVar: RCV000132555, RCV001753519
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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 man with progressive leukoencephalopathy (LKENP; 615889), Dallabona et al. (2014) identified compound heterozygous mutations in the AARS2 gene: a c.2893G-A transition, resulting in a gly965-to-arg (G965R) substitution, and a c.1213G-A transition, resulting in a glu405-to-lys (E405K; 612035.0007) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and were present at a frequency of less than 0.01% in the Exome Variant Server database. Functional studies of the variant were not performed. </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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 LEUKOENCEPHALOPATHY, PROGRESSIVE, WITH OVARIAN FAILURE</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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AARS2, GLU405LYS
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<br />
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SNP: rs587777592,
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gnomAD: rs587777592,
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ClinVar: RCV000132556, RCV001844048
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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 glu405-to-lys (E405K) mutation in the AARS2 gene that was found in compound heterozygous state in a patient with progressive leukoencephalopathy (LKENP; 615889) by Dallabona et al. (2014), see 612035.0006. </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>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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Bonnefond, L., Fender, A., Rudinger-Thirion, J., Giege, R., Florentz, C., Sissler, M.
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<strong>Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS.</strong>
|
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Biochemistry 44: 4805-4816, 2005.
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[PubMed: 15779907]
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[Full Text: https://doi.org/10.1021/bi047527z]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dallabona, C., Diodato, D., Kevelam, S. H., Haack, T. B., Wong, L.-J., Salomons, G. S., Baruffini, E., Melchionda, L., Mariotti, C., Strom, T. M., Meitinger, T., Prokisch, H., and 16 others.
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<strong>Novel (ovario) leukodystrophy related to AARS2 mutations.</strong>
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Neurology 82: 2063-2071, 2014.
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[PubMed: 24808023]
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[Full Text: https://doi.org/10.1212/WNL.0000000000000497]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gotz, A., Tyynismaa, H., Euro, L., Ellonen, P., Hyotylainen, T., Ojala, T., Hamalainen, R. H., Tommiska, J., Raivio, T., Oresic, M., Karikoski, R., Tammela, O., Simola, K. O., Paetau, A., Tyni, T., Suomalainen, A.
|
|
<strong>Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy.</strong>
|
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Am. J. Hum. Genet. 88: 635-642, 2011.
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[PubMed: 21549344]
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[Full Text: https://doi.org/10.1016/j.ajhg.2011.04.006]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Nagase, T., Ishikawa, K., Kikuno, R., Hirosawa, M., Nomura, N., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</strong>
|
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DNA Res. 6: 337-345, 1999.
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[PubMed: 10574462]
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[Full Text: https://doi.org/10.1093/dnares/6.5.337]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Taylor, R. W., Pyle, A., Griffin, H., Blakely, E. L., Duff, J., He, L., Smertenko, T., Alston, C. L., Neeve, V. C., Best, A., Yarham, J. W., Kirschner, J., and 17 others.
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|
<strong>Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.</strong>
|
|
JAMA 312: 68-77, 2014.
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[PubMed: 25058219]
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[Full Text: https://doi.org/10.1001/jama.2014.7184]
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</p>
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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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<div class="row">
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 7/31/2014<br>Cassandra L. Kniffin - updated : 7/19/2011
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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 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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Patricia A. Hartz : 5/8/2008
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mcolton : 07/01/2015<br>alopez : 8/4/2014<br>mcolton : 7/31/2014<br>ckniffin : 7/31/2014<br>wwang : 7/21/2011<br>ckniffin : 7/19/2011<br>mgross : 5/8/2008
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