CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro
Identifieur interne : 001502 ( Istex/Corpus ); précédent : 001501; suivant : 001503CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro
Auteurs : Julie Van Der Zee ; Hazel Urwin ; Sebastiaan Engelborghs ; Marc Bruyland ; Rik Vandenberghe ; Bart Dermaut ; Tim De Pooter ; Karin Peeters ; Patrick Santens ; Peter P. De Deyn ; Elizabeth M. Fisher ; John Collinge ; Adrian M. Isaacs ; Christine Van BroeckhovenSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2008-01-15.
Abstract
The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). In this family, a mutation in the acceptor splice site of exon 6 produced two aberrant transcripts predicting two C-truncated CHMP2B proteins due to a read through of intron 5 (p.Met178ValfsX2) and a cryptic splicing event within exon 6 (p.Met178LeufsX30). Extensive mutation analysis of CHMP2B in Belgian patients (N 146) identified one nonsense mutation in exon 5 (c.493C>T) in a familial FTLD patient, predicting a C-truncated protein p.Gln165X analogous to the Danish mutant proteins. Overexpression of Belgian p.Gln165X in human neuroblastoma SK-N-SH cells showed the formation of large, aberrant endosomal structures that were highly similar to those observed for Danish p.Met178ValfsX2. Together, these data suggest that C-truncating mutations in CHMP2B might underlie the pathogenic mechanism in FTLD by disturbing endosome function. We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive.
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DOI: 10.1093/hmg/ddm309
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De Deyn</name><affiliation><mods:affiliation>Laboratory of Neurochemistry and Behavior, Institute Born-Bunge</mods:affiliation></affiliation><affiliation><mods:affiliation>University of Antwerp</mods:affiliation></affiliation><affiliation><mods:affiliation>Memory Clinic, Department of Neurology, ZNA Middelheim General Hospital, Antwerpen, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Fisher, Elizabeth M" sort="Fisher, Elizabeth M" uniqKey="Fisher E" first="Elizabeth M." last="Fisher">Elizabeth M. Fisher</name><affiliation><mods:affiliation>Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK</mods:affiliation></affiliation></author><author><name sortKey="Collinge, John" sort="Collinge, John" uniqKey="Collinge J" first="John" last="Collinge">John Collinge</name><affiliation><mods:affiliation>MRC Prion Unit</mods:affiliation></affiliation></author><author><name sortKey="Isaacs, Adrian M" sort="Isaacs, Adrian M" uniqKey="Isaacs A" first="Adrian M." last="Isaacs">Adrian M. Isaacs</name><affiliation><mods:affiliation>MRC Prion Unit</mods:affiliation></affiliation></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</mods:affiliation></affiliation><affiliation><mods:affiliation>Laboratory of Neurogenetics</mods:affiliation></affiliation><affiliation><mods:affiliation>University of Antwerp</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: christine.vanbroeckhoven@ua.ac.be</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2008-01-15">2008-01-15</date><biblScope unit="volume">17</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="313">313</biblScope><biblScope unit="page" to="322">322</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">D3956E5DC59E5ABD8D91029F4F5BA33C331F6B94</idno><idno type="DOI">10.1093/hmg/ddm309</idno><idno type="ArticleID">ddm309</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). In this family, a mutation in the acceptor splice site of exon 6 produced two aberrant transcripts predicting two C-truncated CHMP2B proteins due to a read through of intron 5 (p.Met178ValfsX2) and a cryptic splicing event within exon 6 (p.Met178LeufsX30). Extensive mutation analysis of CHMP2B in Belgian patients (N 146) identified one nonsense mutation in exon 5 (c.493C>T) in a familial FTLD patient, predicting a C-truncated protein p.Gln165X analogous to the Danish mutant proteins. Overexpression of Belgian p.Gln165X in human neuroblastoma SK-N-SH cells showed the formation of large, aberrant endosomal structures that were highly similar to those observed for Danish p.Met178ValfsX2. Together, these data suggest that C-truncating mutations in CHMP2B might underlie the pathogenic mechanism in FTLD by disturbing endosome function. We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Julie van der Zee</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</json:string><json:string>Laboratory of Neurogenetics</json:string><json:string>University of Antwerp</json:string></affiliations></json:item><json:item><name>Hazel Urwin</name><affiliations><json:string>MRC Prion Unit</json:string></affiliations></json:item><json:item><name>Sebastiaan Engelborghs</name><affiliations><json:string>Laboratory of Neurochemistry and Behavior, Institute Born-Bunge</json:string><json:string>University of Antwerp</json:string><json:string>Memory Clinic, Department of Neurology, ZNA Middelheim General Hospital, Antwerpen, Belgium</json:string></affiliations></json:item><json:item><name>Marc Bruyland</name><affiliations><json:string>Department of Neurology, AZ Zusters van Barmhartigheid, Ronse, Belgium</json:string></affiliations></json:item><json:item><name>Rik Vandenberghe</name><affiliations><json:string>Department of Neurology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium</json:string></affiliations></json:item><json:item><name>Bart Dermaut</name><affiliations><json:string>Department of Neurology, University Hospital Ghent, University of Ghent, Gent, Belgium</json:string></affiliations></json:item><json:item><name>Tim De Pooter</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</json:string><json:string>Laboratory of Neurogenetics</json:string><json:string>University of Antwerp</json:string></affiliations></json:item><json:item><name>Karin Peeters</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</json:string><json:string>Laboratory of Neurogenetics</json:string><json:string>University of Antwerp</json:string></affiliations></json:item><json:item><name>Patrick Santens</name><affiliations><json:string>Department of Neurology, University Hospital Ghent, University of Ghent, Gent, Belgium</json:string></affiliations></json:item><json:item><name>Peter P. De Deyn</name><affiliations><json:string>Laboratory of Neurochemistry and Behavior, Institute Born-Bunge</json:string><json:string>University of Antwerp</json:string><json:string>Memory Clinic, Department of Neurology, ZNA Middelheim General Hospital, Antwerpen, Belgium</json:string></affiliations></json:item><json:item><name>Elizabeth M. Fisher</name><affiliations><json:string>Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK</json:string></affiliations></json:item><json:item><name>John Collinge</name><affiliations><json:string>MRC Prion Unit</json:string></affiliations></json:item><json:item><name>Adrian M. Isaacs</name><affiliations><json:string>MRC Prion Unit</json:string></affiliations></json:item><json:item><name>Christine Van Broeckhoven</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</json:string><json:string>Laboratory of Neurogenetics</json:string><json:string>University of Antwerp</json:string><json:string>E-mail: christine.vanbroeckhoven@ua.ac.be</json:string></affiliations></json:item></author><articleId><json:string>ddm309</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). In this family, a mutation in the acceptor splice site of exon 6 produced two aberrant transcripts predicting two C-truncated CHMP2B proteins due to a read through of intron 5 (p.Met178ValfsX2) and a cryptic splicing event within exon 6 (p.Met178LeufsX30). Extensive mutation analysis of CHMP2B in Belgian patients (N 146) identified one nonsense mutation in exon 5 (c.493C>T) in a familial FTLD patient, predicting a C-truncated protein p.Gln165X analogous to the Danish mutant proteins. Overexpression of Belgian p.Gln165X in human neuroblastoma SK-N-SH cells showed the formation of large, aberrant endosomal structures that were highly similar to those observed for Danish p.Met178ValfsX2. Together, these data suggest that C-truncating mutations in CHMP2B might underlie the pathogenic mechanism in FTLD by disturbing endosome function. We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. 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xml:id="author-3"><persName><forename type="first">Sebastiaan</forename><surname>Engelborghs</surname></persName><affiliation>Laboratory of Neurochemistry and Behavior, Institute Born-Bunge</affiliation><affiliation>University of Antwerp</affiliation><affiliation>Memory Clinic, Department of Neurology, ZNA Middelheim General Hospital, Antwerpen, Belgium</affiliation></author><author xml:id="author-4"><persName><forename type="first">Marc</forename><surname>Bruyland</surname></persName><affiliation>Department of Neurology, AZ Zusters van Barmhartigheid, Ronse, Belgium</affiliation></author><author xml:id="author-5"><persName><forename type="first">Rik</forename><surname>Vandenberghe</surname></persName><affiliation>Department of Neurology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium</affiliation></author><author xml:id="author-6"><persName><forename type="first">Bart</forename><surname>Dermaut</surname></persName><affiliation>Department of Neurology, University Hospital Ghent, University of Ghent, Gent, Belgium</affiliation></author><author xml:id="author-7"><persName><forename type="first">Tim</forename><surname>De Pooter</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</affiliation><affiliation>Laboratory of Neurogenetics</affiliation><affiliation>University of Antwerp</affiliation></author><author xml:id="author-8"><persName><forename type="first">Karin</forename><surname>Peeters</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</affiliation><affiliation>Laboratory of Neurogenetics</affiliation><affiliation>University of Antwerp</affiliation></author><author xml:id="author-9"><persName><forename type="first">Patrick</forename><surname>Santens</surname></persName><affiliation>Department of Neurology, University Hospital Ghent, University of Ghent, Gent, Belgium</affiliation></author><author xml:id="author-10"><persName><forename type="first">Peter P.</forename><surname>De Deyn</surname></persName><affiliation>Laboratory of Neurochemistry and Behavior, Institute Born-Bunge</affiliation><affiliation>University of Antwerp</affiliation><affiliation>Memory Clinic, Department of Neurology, ZNA Middelheim General Hospital, Antwerpen, Belgium</affiliation></author><author xml:id="author-11"><persName><forename type="first">Elizabeth M.</forename><surname>Fisher</surname></persName><affiliation>Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK</affiliation></author><author xml:id="author-12"><persName><forename type="first">John</forename><surname>Collinge</surname></persName><affiliation>MRC Prion Unit</affiliation></author><author xml:id="author-13"><persName><forename type="first">Adrian M.</forename><surname>Isaacs</surname></persName><affiliation>MRC Prion Unit</affiliation></author><author xml:id="author-14"><persName><forename type="first">Christine</forename><surname>Van Broeckhoven</surname></persName><email>christine.vanbroeckhoven@ua.ac.be</email><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</affiliation><affiliation>Laboratory of Neurogenetics</affiliation><affiliation>University of Antwerp</affiliation></author></analytic><monogr><title level="j">Human Molecular Genetics</title><idno type="pISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2008-01-15"></date><biblScope unit="volume">17</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="313">313</biblScope><biblScope unit="page" to="322">322</biblScope></imprint></monogr><idno type="istex">D3956E5DC59E5ABD8D91029F4F5BA33C331F6B94</idno><idno type="DOI">10.1093/hmg/ddm309</idno><idno type="ArticleID">ddm309</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007-10-22</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). In this family, a mutation in the acceptor splice site of exon 6 produced two aberrant transcripts predicting two C-truncated CHMP2B proteins due to a read through of intron 5 (p.Met178ValfsX2) and a cryptic splicing event within exon 6 (p.Met178LeufsX30). Extensive mutation analysis of CHMP2B in Belgian patients (N 146) identified one nonsense mutation in exon 5 (c.493C>T) in a familial FTLD patient, predicting a C-truncated protein p.Gln165X analogous to the Danish mutant proteins. Overexpression of Belgian p.Gln165X in human neuroblastoma SK-N-SH cells showed the formation of large, aberrant endosomal structures that were highly similar to those observed for Danish p.Met178ValfsX2. Together, these data suggest that C-truncating mutations in CHMP2B might underlie the pathogenic mechanism in FTLD by disturbing endosome function. We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive.</p></abstract></profileDesc><revisionDesc><change when="2007-10-22">Created</change><change when="2008-01-15">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-10-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/D3956E5DC59E5ABD8D91029F4F5BA33C331F6B94/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-id journal-id-type="hwp">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/hmg/ddm309</article-id><article-id pub-id-type="publisher-id">ddm309</article-id><article-categories><subj-group subj-group-type="heading"><subject>ARTICLES</subject></subj-group></article-categories><title-group><article-title><italic>CHMP2B</italic> C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype <italic>in vitro</italic></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>van der Zee</surname><given-names>Julie</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Urwin</surname><given-names>Hazel</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Engelborghs</surname><given-names>Sebastiaan</given-names></name><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Bruyland</surname><given-names>Marc</given-names></name><xref ref-type="aff" rid="af8">8</xref></contrib><contrib contrib-type="author"><name><surname>Vandenberghe</surname><given-names>Rik</given-names></name><xref ref-type="aff" rid="af9">9</xref></contrib><contrib contrib-type="author"><name><surname>Dermaut</surname><given-names>Bart</given-names></name><xref ref-type="aff" rid="af10">10</xref></contrib><contrib contrib-type="author"><name><surname>De Pooter</surname><given-names>Tim</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Peeters</surname><given-names>Karin</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Santens</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="af10">10</xref></contrib><contrib contrib-type="author"><name><surname>De Deyn</surname><given-names>Peter P.</given-names></name><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Fisher</surname><given-names>Elizabeth M.</given-names></name><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Collinge</surname><given-names>John</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Isaacs</surname><given-names>Adrian M.</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Van Broeckhoven</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics</addr-line>, <institution>VIB</institution></aff><aff id="af2"><label>2</label><addr-line>Laboratory of Neurogenetics</addr-line></aff><aff id="af3"><label>3</label><addr-line>Laboratory of Neurochemistry and Behavior</addr-line>, <institution>Institute Born-Bunge</institution></aff><aff id="af4"><label>4</label><institution>University of Antwerp</institution></aff><aff id="af5"><label>5</label><addr-line>Memory Clinic, Department of Neurology</addr-line>, <institution>ZNA Middelheim General Hospital</institution>, <addr-line>Antwerpen</addr-line>, <country>Belgium</country></aff><aff id="af6"><label>6</label><addr-line>MRC Prion Unit</addr-line></aff><aff id="af7"><label>7</label><addr-line>Department of Neurodegenerative Disease</addr-line>, <institution>Institute of Neurology, University College London</institution>, <addr-line>London</addr-line>, <country>UK</country></aff><aff id="af8"><label>8</label><addr-line>Department of Neurology, AZ Zusters van Barmhartigheid, Ronse</addr-line>, <country>Belgium</country></aff><aff id="af9"><label>9</label><addr-line>Department of Neurology</addr-line>, <institution>University Hospital Gasthuisberg, University of Leuven</institution>, <addr-line>Leuven</addr-line>, <country>Belgium</country></aff><aff id="af10"><label>10</label><addr-line>Department of Neurology</addr-line>, <institution>University Hospital Ghent, University of Ghent</institution>, <addr-line>Gent</addr-line>, <country>Belgium</country></aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed at: <addr-line>Department of Molecular Genetics, Neurodegenerative Brain Diseases Group</addr-line>, <institution>VIB University of Antwerp—CDE</institution>, <addr-line>Universiteitsplein 1, BE-2610 Antwerpen</addr-line>, <country>Belgium</country>. Tel: <phone>+32 32651001</phone>; Fax: <fax>+32 32651012</fax>; Email: <email>christine.vanbroeckhoven@ua.ac.be</email></corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>1</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>22</day><month>10</month><year>2007</year></pub-date><volume>17</volume><issue>2</issue><fpage>313</fpage><lpage>322</lpage><history><date date-type="received"><day>11</day><month>7</month><year>2007</year></date><date date-type="accepted"><day>16</day><month>10</month><year>2007</year></date></history><copyright-statement>© 2007 The Author(s)</copyright-statement><copyright-year>2008</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/"><p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</p></license><abstract><p>The charged multivesicular body protein 2B gene (<italic>CHMP2B</italic>) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). In this family, a mutation in the acceptor splice site of exon 6 produced two aberrant transcripts predicting two C-truncated CHMP2B proteins due to a read through of intron 5 (p.Met178ValfsX2) and a cryptic splicing event within exon 6 (p.Met178LeufsX30). Extensive mutation analysis of <italic>CHMP2B</italic> in Belgian patients (<italic>N</italic> = 146) identified one nonsense mutation in exon 5 (c.493C>T) in a familial FTLD patient, predicting a C-truncated protein p.Gln165X analogous to the Danish mutant proteins. Overexpression of Belgian p.Gln165X in human neuroblastoma SK-N-SH cells showed the formation of large, aberrant endosomal structures that were highly similar to those observed for Danish p.Met178ValfsX2. Together, these data suggest that C-truncating mutations in <italic>CHMP2B</italic> might underlie the pathogenic mechanism in FTLD by disturbing endosome function. We also describe a missense mutation in exon 5 of <italic>CHMP2B</italic> (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro</title></titleInfo><name type="personal"><namePart type="given">Julie</namePart><namePart type="family">van der Zee</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</affiliation><affiliation>Laboratory of Neurogenetics</affiliation><affiliation>University of Antwerp</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hazel</namePart><namePart type="family">Urwin</namePart><affiliation>MRC Prion Unit</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sebastiaan</namePart><namePart type="family">Engelborghs</namePart><affiliation>Laboratory of Neurochemistry and Behavior, Institute Born-Bunge</affiliation><affiliation>University of Antwerp</affiliation><affiliation>Memory Clinic, Department of Neurology, ZNA Middelheim General Hospital, Antwerpen, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marc</namePart><namePart type="family">Bruyland</namePart><affiliation>Department of Neurology, AZ Zusters van Barmhartigheid, Ronse, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rik</namePart><namePart type="family">Vandenberghe</namePart><affiliation>Department of Neurology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bart</namePart><namePart type="family">Dermaut</namePart><affiliation>Department of Neurology, University Hospital Ghent, University of Ghent, Gent, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tim</namePart><namePart type="family">De Pooter</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</affiliation><affiliation>Laboratory of Neurogenetics</affiliation><affiliation>University of Antwerp</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karin</namePart><namePart type="family">Peeters</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</affiliation><affiliation>Laboratory of Neurogenetics</affiliation><affiliation>University of Antwerp</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick</namePart><namePart type="family">Santens</namePart><affiliation>Department of Neurology, University Hospital Ghent, University of Ghent, Gent, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter P.</namePart><namePart type="family">De Deyn</namePart><affiliation>Laboratory of Neurochemistry and Behavior, Institute Born-Bunge</affiliation><affiliation>University of Antwerp</affiliation><affiliation>Memory Clinic, Department of Neurology, ZNA Middelheim General Hospital, Antwerpen, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elizabeth M.</namePart><namePart type="family">Fisher</namePart><affiliation>Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John</namePart><namePart type="family">Collinge</namePart><affiliation>MRC Prion Unit</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Adrian M.</namePart><namePart type="family">Isaacs</namePart><affiliation>MRC Prion Unit</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Van Broeckhoven</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</affiliation><affiliation>Laboratory of Neurogenetics</affiliation><affiliation>University of Antwerp</affiliation><affiliation>E-mail: christine.vanbroeckhoven@ua.ac.be</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2008-01-15</dateIssued><dateCreated encoding="w3cdtf">2007-10-22</dateCreated><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>The charged multivesicular body protein 2B gene (CHMP2B) was recently associated with frontotemporal lobar degeneration (FTLD) linked to chromosome 3 in a Danish FTLD family (FTD-3). 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