TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update
Identifieur interne : 001875 ( Istex/Corpus ); précédent : 001874; suivant : 001876TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update
Auteurs : Serena Lattante ; Guy A. Rouleau ; Edor KabashiSource :
- Human Mutation [ 1059-7794 ] ; 2013-06.
Abstract
Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP‐43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP‐43 positive inclusion bodies were first discovered in ubiquitin‐positive, tau‐negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C‐terminus of the proteins. The molecular mechanisms through which mutant TDP‐43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS.
Url:
DOI: 10.1002/humu.22319
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ISTEX:8BAAD7BD7A460528615C61FAE354DB52266454C4Le document en format XML
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Rouleau</name><affiliation><mods:affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</mods:affiliation></affiliation></author><author><name sortKey="Kabashi, Edor" sort="Kabashi, Edor" uniqKey="Kabashi E" first="Edor" last="Kabashi">Edor Kabashi</name><affiliation><mods:affiliation>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: edor.kabashi@icm-institute.org</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:8BAAD7BD7A460528615C61FAE354DB52266454C4</idno><date when="2013" year="2013">2013</date><idno type="doi">10.1002/humu.22319</idno><idno type="url">https://api-v5.istex.fr/document/8BAAD7BD7A460528615C61FAE354DB52266454C4/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001875</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001875</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update</title><author><name sortKey="Lattante, Serena" sort="Lattante, Serena" uniqKey="Lattante S" first="Serena" last="Lattante">Serena Lattante</name><affiliation><mods:affiliation>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Rouleau, Guy A" sort="Rouleau, Guy A" uniqKey="Rouleau G" first="Guy A." last="Rouleau">Guy A. Rouleau</name><affiliation><mods:affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</mods:affiliation></affiliation></author><author><name sortKey="Kabashi, Edor" sort="Kabashi, Edor" uniqKey="Kabashi E" first="Edor" last="Kabashi">Edor Kabashi</name><affiliation><mods:affiliation>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: edor.kabashi@icm-institute.org</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Mutation</title><title level="j" type="abbrev">Human Mutation</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-06">2013-06</date><biblScope unit="volume">34</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="812">812</biblScope><biblScope unit="page" to="826">826</biblScope></imprint><idno type="ISSN">1059-7794</idno></series><idno type="istex">8BAAD7BD7A460528615C61FAE354DB52266454C4</idno><idno type="DOI">10.1002/humu.22319</idno><idno type="ArticleID">HUMU22319</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP‐43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP‐43 positive inclusion bodies were first discovered in ubiquitin‐positive, tau‐negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C‐terminus of the proteins. The molecular mechanisms through which mutant TDP‐43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Serena Lattante</name><affiliations><json:string>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</json:string></affiliations></json:item><json:item><name>Guy A. Rouleau</name><affiliations><json:string>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</json:string></affiliations></json:item><json:item><name>Edor Kabashi</name><affiliations><json:string>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</json:string><json:string>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</json:string><json:string>E-mail: edor.kabashi@icm-institute.org</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>amyotrophic lateral sclerosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>frontotemporal lobar degeneration</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TARDBP</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>FUS</value></json:item></subject><articleId><json:string>HUMU22319</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Amyotrophic Lateral Sclerosis is a progressive and devastating disorder of motor neurons. A number of genes have been found commonly mutated in ALS patients. Among these, TARDBP and FUS play an important role. Both proteins are involved in mRNA transport, axonal maintenance and motor neuron development but the exact molecular mechanisms through which they cause motor neuron degeneration, when mutated, are not well understood. This report summarizes the genetic, biological and clinical relevance of TARDBP and FUS mutations in ALS.</abstract><qualityIndicators><score>7.58</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.245 x 793.92 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1468</abstractCharCount><pdfWordCount>14192</pdfWordCount><pdfCharCount>88259</pdfCharCount><pdfPageCount>15</pdfPageCount><abstractWordCount>215</abstractWordCount></qualityIndicators><title>TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update</title><genre><json:string>article</json:string></genre><host><title>Human Mutation</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1098-1004</json:string></doi><issn><json:string>1059-7794</json:string></issn><eissn><json:string>1098-1004</json:string></eissn><publisherId><json:string>HUMU</json:string></publisherId><volume>34</volume><issue>6</issue><pages><first>812</first><last>826</last><total>15</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Mutation Update</value></json:item></subject></host><categories><wos><json:string>science</json:string><json:string>genetics & heredity</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>biomedical research</json:string><json:string>genetics & heredity</json:string></scienceMetrix><inist><json:string>sciences appliquees, technologies et medecines</json:string><json:string>sciences biologiques et medicales</json:string><json:string>sciences medicales</json:string></inist></categories><publicationDate>2013</publicationDate><copyrightDate>2013</copyrightDate><doi><json:string>10.1002/humu.22319</json:string></doi><id>8BAAD7BD7A460528615C61FAE354DB52266454C4</id><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api-v5.istex.fr/document/8BAAD7BD7A460528615C61FAE354DB52266454C4/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api-v5.istex.fr/document/8BAAD7BD7A460528615C61FAE354DB52266454C4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api-v5.istex.fr/document/8BAAD7BD7A460528615C61FAE354DB52266454C4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><availability><p>Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company© 2013 Wiley Periodicals, Inc.</p></availability><date>2013-04-01</date></publicationStmt><notesStmt><note>Atip/Avenir from Inserm</note><note>Career Integration Grant (ERC)</note><note>Robert Packard Foundation</note><note>AFM</note><note>ARSLA</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update</title><author xml:id="author-1"><persName><forename type="first">Serena</forename><surname>Lattante</surname></persName><affiliation>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">Guy A.</forename><surname>Rouleau</surname></persName><affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</affiliation></author><author xml:id="author-3"><persName><forename type="first">Edor</forename><surname>Kabashi</surname></persName><email>edor.kabashi@icm-institute.org</email><affiliation>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</affiliation><affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</affiliation></author></analytic><monogr><title level="j">Human Mutation</title><title level="j" type="abbrev">Human Mutation</title><idno type="pISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><idno type="DOI">10.1002/(ISSN)1098-1004</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-06"></date><biblScope unit="volume">34</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="812">812</biblScope><biblScope unit="page" to="826">826</biblScope></imprint></monogr><idno type="istex">8BAAD7BD7A460528615C61FAE354DB52266454C4</idno><idno type="DOI">10.1002/humu.22319</idno><idno type="ArticleID">HUMU22319</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2013-04-01</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP‐43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP‐43 positive inclusion bodies were first discovered in ubiquitin‐positive, tau‐negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C‐terminus of the proteins. The molecular mechanisms through which mutant TDP‐43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS.</p></abstract><abstract xml:lang="en" style="graphical"><p>Amyotrophic Lateral Sclerosis is a progressive and devastating disorder of motor neurons. A number of genes have been found commonly mutated in ALS patients. Among these, TARDBP and FUS play an important role. Both proteins are involved in mRNA transport, axonal maintenance and motor neuron development but the exact molecular mechanisms through which they cause motor neuron degeneration, when mutated, are not well understood. This report summarizes the genetic, biological and clinical relevance of TARDBP and FUS mutations in ALS.</p></abstract><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>amyotrophic lateral sclerosis</term></item><item><term>frontotemporal lobar degeneration</term></item><item><term>TARDBP</term></item><item><term>FUS</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Mutation Update</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2012-12-13">Received</change><change when="2013-02-28">Registration</change><change when="2013-04-01">Created</change><change when="2013-06">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api-v5.istex.fr/document/8BAAD7BD7A460528615C61FAE354DB52266454C4/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en" xml:id="HUMU22319"><header><publicationMeta level="product"><doi origin="wiley" registered="yes">10.1002/(ISSN)1098-1004</doi><issn type="print">1059-7794</issn><issn type="electronic">1098-1004</issn><idGroup><id type="product" value="HUMU"></id></idGroup><titleGroup><title type="main" sort="HUMAN MUTATION">Human Mutation</title><title type="short">Human Mutation</title></titleGroup></publicationMeta><publicationMeta level="part" position="06106"><doi>10.1002/humu.2013.34.issue-6</doi><copyright ownership="publisher">Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company</copyright><numberingGroup><numbering type="journalVolume" number="34">34</numbering><numbering type="journalIssue">6</numbering></numberingGroup><coverDate startDate="2013-06">June 2013</coverDate></publicationMeta><publicationMeta level="unit" position="40" type="article" status="forIssue"><doi origin="wiley">10.1002/humu.22319</doi><idGroup><id type="unit" value="HUMU22319"></id></idGroup><countGroup><count type="pageTotal" number="15"></count></countGroup><titleGroup><title type="articleCategory">Mutation Update</title><title type="tocHeading1">Mutation Updates</title></titleGroup><copyright ownership="publisher">© 2013 Wiley Periodicals, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2012-12-13"></event><event type="manuscriptAccepted" date="2013-02-28"></event><event type="xmlCreated" agent="Aptara" date="2013-04-01"></event><event type="publishedOnlineAccepted" date="2013-04-04"></event><event type="publishedOnlineEarlyUnpaginated" date="2013-04-29"></event><event type="firstOnline" date="2013-04-29"></event><event type="publishedOnlineFinalForm" date="2013-05-20"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-27"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.6.4 mode:FullText" date="2015-10-04"></event></eventGroup><numberingGroup><numbering type="pageFirst">812</numbering><numbering type="pageLast">826</numbering></numberingGroup><correspondenceTo>Correspondence to: Edor Kabashi, Hôpital Pitié‐Salpêtrière, Université Pierre et Marie Curie‐Paris, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, 75013 Paris, France. E‐mail: <email>edor.kabashi@icm-institute.org</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:HUMU.HUMU22319.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main"><i>TARDBP</i> and <i>FUS</i> Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update</title></titleGroup><creators><creator xml:id="humu22319-cr-0001" creatorRole="author" affiliationRef="#humu22319-aff-0001"><personName><givenNames>Serena</givenNames><familyName>Lattante</familyName></personName></creator><creator xml:id="humu22319-cr-0002" creatorRole="author" affiliationRef="#humu22319-aff-0002"><personName><givenNames>Guy A.</givenNames><familyName>Rouleau</familyName></personName></creator><creator xml:id="humu22319-cr-0003" creatorRole="author" affiliationRef="#humu22319-aff-0001 #humu22319-aff-0002" corresponding="yes"><personName><givenNames>Edor</givenNames><familyName>Kabashi</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="humu22319-aff-0001" countryCode="FR"><orgDiv>Institut du Cerveau et de la Moelle épinière</orgDiv><orgName>Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225</orgName><address><postCode>F‐75013</postCode><city>Paris</city><country>France</country></address></affiliation><affiliation xml:id="humu22319-aff-0002" countryCode="CA"><orgDiv>Montreal Neurological Institute</orgDiv><orgName>Department of Neurology and Neurosurgery, McGill University</orgName><address><city>Montreal</city><country>Canada</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="humu22319-kwd-0001">amyotrophic lateral sclerosis</keyword><keyword xml:id="humu22319-kwd-0002">frontotemporal lobar degeneration</keyword><keyword xml:id="humu22319-kwd-0003"><fc>TARDBP</fc></keyword><keyword xml:id="humu22319-kwd-0004"><fc>FUS</fc></keyword></keywordGroup><fundingInfo><fundingAgency>Atip/Avenir from Inserm</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Career Integration Grant (ERC)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Robert Packard Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>AFM</fundingAgency></fundingInfo><fundingInfo><fundingAgency>ARSLA</fundingAgency></fundingInfo><abstractGroup><abstract type="main"><title type="main">ABSTRACT</title><p>Mutations in the <fc>TAR DNA B</fc>inding <fc>P</fc>rotein gene (<i>TARDBP</i>), encoding the protein <fc>TDP</fc>‐43, were identified in amyotrophic lateral sclerosis (<fc>ALS</fc>) patients. Interestingly, <fc>TDP</fc>‐43 positive inclusion bodies were first discovered in ubiquitin‐positive, tau‐negative <fc>ALS</fc> and frontotemporal dementia (<fc>FTD</fc>) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (<fc>FALS</fc>) and sporadic (<fc>SALS</fc>) patients. Fused in sarcoma (<i>FUS</i>) was found to be responsible for a previously identified <fc>ALS</fc>6 locus, being mutated in both <fc>FALS</fc> and <fc>SALS</fc> patients. <i>TARDBP</i> and <i>FUS</i> have a structural and functional similarity and most of mutations in both genes are also clustered in the <fc>C</fc>‐terminus of the proteins. The molecular mechanisms through which mutant <fc>TDP</fc>‐43 and <fc>FUS</fc> may cause motor neuron degeneration are not well understood. Both proteins play an important role in m<fc>RNA</fc> transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of <i>TARDBP</i> and <i>FUS</i> mutations in <fc>ALS</fc>. All the data reviewed here have been submitted to a database based on the <fc>L</fc>eiden <fc>O</fc>pen (source) <fc>V</fc>ariation <fc>D</fc>atabase (<fc>LOVD</fc>) and is accessible online at <url href="http://www.lovd.nl/TARDBP">www.lovd.nl/TARDBP</url>, <url href="http://www.lovd.nl/FUS">www.lovd.nl/FUS</url>.</p></abstract><abstract xml:id="humu22319-abs-0001" type="graphical" xml:lang="en"><p>Amyotrophic Lateral Sclerosis is a progressive and devastating disorder of motor neurons. A number of genes have been found commonly mutated in ALS patients. Among these, <i>TARDBP</i> and <i>FUS</i> play an important role. Both proteins are involved in mRNA transport, axonal maintenance and motor neuron development but the exact molecular mechanisms through which they cause motor neuron degeneration, when mutated, are not well understood. This report summarizes the genetic, biological and clinical relevance of <i>TARDBP</i> and <i>FUS</i> mutations in ALS. <blockFixed type="graphic"><mediaResourceGroup><mediaResource alt="image" href="urn:x-wiley:10597794:media:humu22319:humu22319-gra-0001"></mediaResource></mediaResourceGroup></blockFixed></p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="humu22319-note-0001" numbered="no"><p>Communicated by Mireille Clustres</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>TARDBP and FUS Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update</title></titleInfo><name type="personal"><namePart type="given">Serena</namePart><namePart type="family">Lattante</namePart><affiliation>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Guy A.</namePart><namePart type="family">Rouleau</namePart><affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Edor</namePart><namePart type="family">Kabashi</namePart><affiliation>Institut du Cerveau et de la Moelle épinière, Centre de Recherche, CHU Pitié‐Salpétrière, Inserm, UMR_S975, CRICM, F‐75013; UPMC Univ Paris 06, UMR_S975, F‐75013; CNRS UMR 7225, F‐75013, Paris, France</affiliation><affiliation>Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada</affiliation><affiliation>E-mail: edor.kabashi@icm-institute.org</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2013-06</dateIssued><dateCreated encoding="w3cdtf">2013-04-01</dateCreated><dateCaptured encoding="w3cdtf">2012-12-13</dateCaptured><dateValid encoding="w3cdtf">2013-02-28</dateValid><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP‐43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP‐43 positive inclusion bodies were first discovered in ubiquitin‐positive, tau‐negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C‐terminus of the proteins. The molecular mechanisms through which mutant TDP‐43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS.</abstract><abstract type="graphical" lang="en">Amyotrophic Lateral Sclerosis is a progressive and devastating disorder of motor neurons. A number of genes have been found commonly mutated in ALS patients. Among these, TARDBP and FUS play an important role. Both proteins are involved in mRNA transport, axonal maintenance and motor neuron development but the exact molecular mechanisms through which they cause motor neuron degeneration, when mutated, are not well understood. This report summarizes the genetic, biological and clinical relevance of TARDBP and FUS mutations in ALS.</abstract><note type="funding">Atip/Avenir from Inserm</note><note type="funding">Career Integration Grant (ERC)</note><note type="funding">Robert Packard Foundation</note><note type="funding">AFM</note><note type="funding">ARSLA</note><subject><genre>keywords</genre><topic>amyotrophic lateral sclerosis</topic><topic>frontotemporal lobar degeneration</topic><topic>TARDBP</topic><topic>FUS</topic></subject><relatedItem type="host"><titleInfo><title>Human Mutation</title></titleInfo><titleInfo type="abbreviated"><title>Human Mutation</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Mutation Update</topic></subject><identifier type="ISSN">1059-7794</identifier><identifier type="eISSN">1098-1004</identifier><identifier type="DOI">10.1002/(ISSN)1098-1004</identifier><identifier type="PublisherID">HUMU</identifier><part><date>2013</date><detail type="volume"><caption>vol.</caption><number>34</number></detail><detail type="issue"><caption>no.</caption><number>6</number></detail><extent unit="pages"><start>812</start><end>826</end><total>15</total></extent></part></relatedItem><identifier type="istex">8BAAD7BD7A460528615C61FAE354DB52266454C4</identifier><identifier type="DOI">10.1002/humu.22319</identifier><identifier type="ArticleID">HUMU22319</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company© 2013 Wiley Periodicals, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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