A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD
Identifieur interne : 000A01 ( Istex/Corpus ); précédent : 000A00; suivant : 000A02A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD
Auteurs : Julie Van Der Zee ; Rosa Rademakers ; Sebastiaan Engelborghs ; Ilse Gijselinck ; Veerle Bogaerts ; Rik Vandenberghe ; Patrick Santens ; Jo Caekebeke ; Tim De Pooter ; Karin Peeters ; Ursula Lu Bke ; Marleen Van Den Broeck ; Jean-Jacques Martin ; Marc Cruts ; Peter P. De Deyn ; Christine Van Broeckhoven ; Bart DermautSource :
- Brain [ 0006-8950 ] ; 2006-04.
English descriptors
- KwdEn :
Abstract
Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to MAPT mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM MAPT containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable MAPT mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2–DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2–DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than MAPT mutations (1 out of 98 or 1%). Clinically, DR2–DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2–DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations.
Url:
DOI: 10.1093/brain/awl029
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<author><name sortKey="Caekebeke, Jo" sort="Caekebeke, Jo" uniqKey="Caekebeke J" first="Jo" last="Caekebeke">Jo Caekebeke</name>
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<author><name sortKey="Peeters, Karin" sort="Peeters, Karin" uniqKey="Peeters K" first="Karin" last="Peeters">Karin Peeters</name>
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<author><name sortKey="Lu Bke, Ursula" sort="Lu Bke, Ursula" uniqKey="Lu Bke U" first="Ursula" last="Lu Bke">Ursula Lu Bke</name>
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<author><name sortKey="Van Den Broeck, Marleen" sort="Van Den Broeck, Marleen" uniqKey="Van Den Broeck M" first="Marleen" last="Van Den Broeck">Marleen Van Den Broeck</name>
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<author><name sortKey="Martin, Jean Jacques" sort="Martin, Jean Jacques" uniqKey="Martin J" first="Jean-Jacques" last="Martin">Jean-Jacques Martin</name>
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<author><name sortKey="De Deyn, Peter P" sort="De Deyn, Peter P" uniqKey="De Deyn P" first="Peter P." last="De Deyn">Peter P. De Deyn</name>
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<author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name>
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<author><name sortKey="Dermaut, Bart" sort="Dermaut, Bart" uniqKey="Dermaut B" first="Bart" last="Dermaut">Bart Dermaut</name>
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<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD</title>
<author><name sortKey="Van Der Zee, Julie" sort="Van Der Zee, Julie" uniqKey="Van Der Zee J" first="Julie" last="Van Der Zee">Julie Van Der Zee</name>
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<author><name sortKey="Rademakers, Rosa" sort="Rademakers, Rosa" uniqKey="Rademakers R" first="Rosa" last="Rademakers">Rosa Rademakers</name>
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<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
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<author><name sortKey="Engelborghs, Sebastiaan" sort="Engelborghs, Sebastiaan" uniqKey="Engelborghs S" first="Sebastiaan" last="Engelborghs">Sebastiaan Engelborghs</name>
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<author><name sortKey="Gijselinck, Ilse" sort="Gijselinck, Ilse" uniqKey="Gijselinck I" first="Ilse" last="Gijselinck">Ilse Gijselinck</name>
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<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
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<author><name sortKey="Vandenberghe, Rik" sort="Vandenberghe, Rik" uniqKey="Vandenberghe R" first="Rik" last="Vandenberghe">Rik Vandenberghe</name>
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<author><name sortKey="Santens, Patrick" sort="Santens, Patrick" uniqKey="Santens P" first="Patrick" last="Santens">Patrick Santens</name>
<affiliation><mods:affiliation>Department of Neurology, Ghent University Hospital, University of Ghent,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
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<author><name sortKey="Caekebeke, Jo" sort="Caekebeke, Jo" uniqKey="Caekebeke J" first="Jo" last="Caekebeke">Jo Caekebeke</name>
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</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
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<author><name sortKey="De Pooter, Tim" sort="De Pooter, Tim" uniqKey="De Pooter T" first="Tim" last="De Pooter">Tim De Pooter</name>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
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<author><name sortKey="Peeters, Karin" sort="Peeters, Karin" uniqKey="Peeters K" first="Karin" last="Peeters">Karin Peeters</name>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
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<author><name sortKey="Lu Bke, Ursula" sort="Lu Bke, Ursula" uniqKey="Lu Bke U" first="Ursula" last="Lu Bke">Ursula Lu Bke</name>
<affiliation><mods:affiliation>Laboratory of Neuropathology, Institute Born-Bunge, University of Antwerp,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Van Den Broeck, Marleen" sort="Van Den Broeck, Marleen" uniqKey="Van Den Broeck M" first="Marleen" last="Van Den Broeck">Marleen Van Den Broeck</name>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Martin, Jean Jacques" sort="Martin, Jean Jacques" uniqKey="Martin J" first="Jean-Jacques" last="Martin">Jean-Jacques Martin</name>
<affiliation><mods:affiliation>Laboratory of Neuropathology, Institute Born-Bunge, University of Antwerp,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Cruts, Marc" sort="Cruts, Marc" uniqKey="Cruts M" first="Marc" last="Cruts">Marc Cruts</name>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="De Deyn, Peter P" sort="De Deyn, Peter P" uniqKey="De Deyn P" first="Peter P." last="De Deyn">Peter P. De Deyn</name>
<affiliation><mods:affiliation>Laboratory of Neurochemistry and Behavior,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Dermaut, Bart" sort="Dermaut, Bart" uniqKey="Dermaut B" first="Bart" last="Dermaut">Bart Dermaut</name>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</mods:affiliation>
</affiliation>
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<series><title level="j">Brain</title>
<title level="j" type="abbrev">Brain</title>
<idno type="ISSN">0006-8950</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>17q21, tau-negative</term>
<term>DLDH, dementia lacking distinctive histopathology</term>
<term>FTDU = FTLD with tau-negative and ubiquitin-positive inclusions</term>
<term>FTLD = frontotemporal lobar degeneration</term>
<term>LOD = log of the odds</term>
<term>founder mutation</term>
<term>frontotemporal lobar degeneration</term>
<term>ubiquitin-positive</term>
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<front><div type="abstract" xml:lang="en">Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to MAPT mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM MAPT containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable MAPT mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2–DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2–DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than MAPT mutations (1 out of 98 or 1%). Clinically, DR2–DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2–DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations.</div>
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<json:item><name>Ursula Lübke</name>
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<notesStmt><note>Correspondence to: Prof. Dr Christine Van Broeckhoven, Neurodegenerative Brain Diseases Group, VIB8 Department of Molecular Genetics, University of Antwerp, Building V, Room 0.10, Universiteitsplein 1, BE-2610 Antwerpen, Belgium E-mail: christine.vanbroeckhoven@ua.ac.be</note>
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<author xml:id="author-9"><persName><forename type="first">Tim</forename>
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<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
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<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
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<author xml:id="author-11"><persName><forename type="first">Ursula</forename>
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<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
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<author xml:id="author-13"><persName><forename type="first">Jean-Jacques</forename>
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<surname>Dermaut</surname>
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<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
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<abstract xml:lang="en"><p>Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to MAPT mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM MAPT containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable MAPT mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2–DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2–DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than MAPT mutations (1 out of 98 or 1%). Clinically, DR2–DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2–DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations.</p>
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<title-group><article-title>A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>van der Zee</surname>
<given-names>Julie</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rademakers</surname>
<given-names>Rosa</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Engelborghs</surname>
<given-names>Sebastiaan</given-names>
</name>
<xref rid="AFF2">2</xref>
<xref rid="AFF6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gijselinck</surname>
<given-names>Ilse</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bogaerts</surname>
<given-names>Veerle</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vandenberghe</surname>
<given-names>Rik</given-names>
</name>
<xref rid="AFF5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Santens</surname>
<given-names>Patrick</given-names>
</name>
<xref rid="AFF4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Caekebeke</surname>
<given-names>Jo</given-names>
</name>
<xref rid="AFF7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>De Pooter</surname>
<given-names>Tim</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peeters</surname>
<given-names>Karin</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lübke</surname>
<given-names>Ursula</given-names>
</name>
<xref rid="AFF3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Van den Broeck</surname>
<given-names>Marleen</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Martin</surname>
<given-names>Jean-Jacques</given-names>
</name>
<xref rid="AFF3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cruts</surname>
<given-names>Marc</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>De Deyn</surname>
<given-names>Peter P.</given-names>
</name>
<xref rid="AFF2">2</xref>
<xref rid="AFF6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Van Broeckhoven</surname>
<given-names>Christine</given-names>
</name>
<xref rid="AFF1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dermaut</surname>
<given-names>Bart</given-names>
</name>
<xref rid="AFF1">1</xref>
<xref rid="AFF4">4</xref>
</contrib>
<aff><target target-type="aff" id="AFF1"></target>
<label>1</label>
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, <target target-type="aff" id="AFF2"></target>
<label>2</label>
Laboratory of Neurochemistry and Behavior, <target target-type="aff" id="AFF3"></target>
<label>3</label>
Laboratory of Neuropathology, Institute Born-Bunge, University of Antwerp, <target target-type="aff" id="AFF4"></target>
<label>4</label>
Department of Neurology, Ghent University Hospital, University of Ghent, <target target-type="aff" id="AFF5"></target>
<label>5</label>
Department of Neurology, University Hospital Gasthuisberg, Catholic University of Leuven, <target target-type="aff" id="AFF6"></target>
<label>6</label>
Department of Neurology and Memory Clinic, Middelheim General Hospital, Antwerp and <target target-type="aff" id="AFF7"></target>
<label>7</label>
Department of Neurology, OLV Hospital Aalst, Belgium</aff>
</contrib-group>
<author-notes><corresp>Correspondence to: Prof. Dr Christine Van Broeckhoven, Neurodegenerative Brain Diseases Group, VIB8 Department of Molecular Genetics, University of Antwerp, Building V, Room 0.10, Universiteitsplein 1, BE-2610 Antwerpen, Belgium E-mail: <ext-link xlink:href="christine.vanbroeckhoven@ua.ac.be" ext-link-type="email">christine.vanbroeckhoven@ua.ac.be</ext-link>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>April</month>
<year>2006</year>
</pub-date>
<pub-date pub-type="epub"><day>22</day>
<month>2</month>
<year>2006</year>
</pub-date>
<volume>129</volume>
<issue>4</issue>
<fpage>841</fpage>
<lpage>852</lpage>
<history><date date-type="accepted"><day>16</day>
<month>1</month>
<year>2006</year>
</date>
<date date-type="received"><day>5</day>
<month>9</month>
<year>2005</year>
</date>
<date date-type="rev-recd"><day>11</day>
<month>1</month>
<year>2006</year>
</date>
</history>
<copyright-statement>© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement>
<copyright-year>2006</copyright-year>
<license license-type="open-access"><p></p>
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<abstract xml:lang="en"><p>Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to <italic>MAPT</italic>
mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM <italic>MAPT</italic>
containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable <italic>MAPT</italic>
mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2–DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2–DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than <italic>MAPT</italic>
mutations (1 out of 98 or 1%). Clinically, DR2–DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2–DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than <italic>MAPT</italic>
mutations.</p>
</abstract>
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<kwd>FTDU = FTLD with tau-negative and ubiquitin-positive inclusions</kwd>
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<mods version="3.6"><titleInfo lang="en"><title>A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD</title>
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<titleInfo type="alternative" lang="en" contentType="CDATA"><title>A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD</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, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Rosa</namePart>
<namePart type="family">Rademakers</namePart>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Ilse</namePart>
<namePart type="family">Gijselinck</namePart>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Veerle</namePart>
<namePart type="family">Bogaerts</namePart>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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, Catholic University of Leuven,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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, Ghent University Hospital, University of Ghent,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Jo</namePart>
<namePart type="family">Caekebeke</namePart>
<affiliation>Department of Neurology, OLV Hospital Aalst, Belgium</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Ursula</namePart>
<namePart type="family">Lübke</namePart>
<affiliation>Laboratory of Neuropathology, Institute Born-Bunge, University of Antwerp,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Marleen</namePart>
<namePart type="family">Van den Broeck</namePart>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Jean-Jacques</namePart>
<namePart type="family">Martin</namePart>
<affiliation>Laboratory of Neuropathology, Institute Born-Bunge, University of Antwerp,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Marc</namePart>
<namePart type="family">Cruts</namePart>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</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, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Bart</namePart>
<namePart type="family">Dermaut</namePart>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology,</affiliation>
<role><roleTerm type="text">author</roleTerm>
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<dateIssued encoding="w3cdtf">2006-04</dateIssued>
<dateCreated encoding="w3cdtf">2006-02-22</dateCreated>
<copyrightDate encoding="w3cdtf">2006</copyrightDate>
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<abstract lang="en">Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to MAPT mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM MAPT containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable MAPT mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2–DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2–DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than MAPT mutations (1 out of 98 or 1%). Clinically, DR2–DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2–DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations.</abstract>
<note type="author-notes">Correspondence to: Prof. Dr Christine Van Broeckhoven, Neurodegenerative Brain Diseases Group, VIB8 Department of Molecular Genetics, University of Antwerp, Building V, Room 0.10, Universiteitsplein 1, BE-2610 Antwerpen, Belgium E-mail: christine.vanbroeckhoven@ua.ac.be</note>
<subject lang="en"><genre>KWD</genre>
<topic>founder mutation</topic>
<topic>frontotemporal lobar degeneration</topic>
<topic>ubiquitin-positive</topic>
<topic>17q21, tau-negative</topic>
</subject>
<subject lang="en"><genre>ABR</genre>
<topic>FTLD = frontotemporal lobar degeneration</topic>
<topic>FTDU = FTLD with tau-negative and ubiquitin-positive inclusions</topic>
<topic>DLDH, dementia lacking distinctive histopathology</topic>
<topic>LOD = log of the odds</topic>
</subject>
<relatedItem type="host"><titleInfo><title>Brain</title>
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<titleInfo type="abbreviated"><title>Brain</title>
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<genre type="journal">journal</genre>
<identifier type="ISSN">0006-8950</identifier>
<identifier type="eISSN">1460-2156</identifier>
<identifier type="PublisherID">brainj</identifier>
<identifier type="PublisherID-hwp">brain</identifier>
<identifier type="PublisherID-nlm-ta">Brain</identifier>
<part><date>2006</date>
<detail type="volume"><caption>vol.</caption>
<number>129</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>4</number>
</detail>
<extent unit="pages"><start>841</start>
<end>852</end>
</extent>
</part>
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<identifier type="istex">C19CFA2C3EE2AA9D3C849A26CAF23B6A50952BDE</identifier>
<identifier type="DOI">10.1093/brain/awl029</identifier>
<identifier type="local">awl029</identifier>
<accessCondition type="use and reproduction" contentType="copyright">© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</accessCondition>
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