A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD
Identifieur interne : 001691 ( Main/Exploration ); précédent : 001690; suivant : 001692A 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 [Belgique] ; Tim De Pooter ; Karin Peeters ; Ursula Lu Bke [Belgique] ; Marleen Van Den Broeck ; Jean-Jacques Martin [Belgique] ; Marc Cruts ; Peter P. De Deyn ; Christine Van Broeckhoven ; Bart DermautSource :
- Brain [ 0006-8950 ] ; 2006-04.
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- 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.
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DOI: 10.1093/brain/awl029
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Engelborghs</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Gijselinck, Ilse" sort="Gijselinck, Ilse" uniqKey="Gijselinck I" first="Ilse" last="Gijselinck">Ilse Gijselinck</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Bogaerts, Veerle" sort="Bogaerts, Veerle" uniqKey="Bogaerts V" first="Veerle" last="Bogaerts">Veerle Bogaerts</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Vandenberghe, Rik" sort="Vandenberghe, Rik" uniqKey="Vandenberghe R" first="Rik" last="Vandenberghe">Rik Vandenberghe</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Santens, Patrick" sort="Santens, Patrick" uniqKey="Santens P" first="Patrick" last="Santens">Patrick Santens</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Caekebeke, Jo" sort="Caekebeke, Jo" uniqKey="Caekebeke J" first="Jo" last="Caekebeke">Jo Caekebeke</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Neurology, OLV Hospital Aalst</wicri:regionArea><wicri:noRegion>OLV Hospital Aalst</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="De Pooter, Tim" sort="De Pooter, Tim" uniqKey="De Pooter T" first="Tim" last="De Pooter">Tim De Pooter</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Peeters, Karin" sort="Peeters, Karin" uniqKey="Peeters K" first="Karin" last="Peeters">Karin Peeters</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Lu Bke, Ursula" sort="Lu Bke, Ursula" uniqKey="Lu Bke U" first="Ursula" last="Lu Bke">Ursula Lu Bke</name><affiliation wicri:level="4"><country>Belgique</country><placeName><settlement type="city">Anvers</settlement><region type="district" nuts="2">Province d'Anvers</region></placeName><orgName type="university">Université d'Anvers</orgName></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></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></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></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 wicri:level="4"><country>Belgique</country><placeName><settlement type="city">Anvers</settlement><region type="district" nuts="2">Province d'Anvers</region></placeName><orgName type="university">Université d'Anvers</orgName></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Cruts, Marc" sort="Cruts, Marc" uniqKey="Cruts M" first="Marc" last="Cruts">Marc Cruts</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></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></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></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></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Dermaut, Bart" sort="Dermaut, Bart" uniqKey="Dermaut B" first="Bart" last="Dermaut">Bart Dermaut</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><title level="j" type="abbrev">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2006-04">2006-04</date><biblScope unit="volume">129</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="841">841</biblScope><biblScope unit="page" to="852">852</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">C19CFA2C3EE2AA9D3C849A26CAF23B6A50952BDE</idno><idno type="DOI">10.1093/brain/awl029</idno><idno type="local">awl029</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><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></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><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></front></TEI><affiliations><list><country><li>Belgique</li></country><region><li>Province d'Anvers</li></region><settlement><li>Anvers</li></settlement><orgName><li>Université d'Anvers</li></orgName></list><tree><noCountry><name sortKey="Bogaerts, Veerle" sort="Bogaerts, Veerle" uniqKey="Bogaerts V" first="Veerle" last="Bogaerts">Veerle Bogaerts</name><name sortKey="Cruts, Marc" sort="Cruts, Marc" uniqKey="Cruts M" first="Marc" last="Cruts">Marc Cruts</name><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><name sortKey="De Pooter, Tim" sort="De Pooter, Tim" uniqKey="De Pooter T" first="Tim" last="De Pooter">Tim De Pooter</name><name sortKey="Dermaut, Bart" sort="Dermaut, Bart" uniqKey="Dermaut B" first="Bart" last="Dermaut">Bart Dermaut</name><name sortKey="Engelborghs, Sebastiaan" sort="Engelborghs, Sebastiaan" uniqKey="Engelborghs S" first="Sebastiaan" last="Engelborghs">Sebastiaan Engelborghs</name><name sortKey="Gijselinck, Ilse" sort="Gijselinck, Ilse" uniqKey="Gijselinck I" first="Ilse" last="Gijselinck">Ilse Gijselinck</name><name sortKey="Peeters, Karin" sort="Peeters, Karin" uniqKey="Peeters K" first="Karin" last="Peeters">Karin Peeters</name><name sortKey="Rademakers, Rosa" sort="Rademakers, Rosa" uniqKey="Rademakers R" first="Rosa" last="Rademakers">Rosa Rademakers</name><name sortKey="Santens, Patrick" sort="Santens, Patrick" uniqKey="Santens P" first="Patrick" last="Santens">Patrick Santens</name><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><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><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><name sortKey="Vandenberghe, Rik" sort="Vandenberghe, Rik" uniqKey="Vandenberghe R" first="Rik" last="Vandenberghe">Rik Vandenberghe</name></noCountry><country name="Belgique"><noRegion><name sortKey="Caekebeke, Jo" sort="Caekebeke, Jo" uniqKey="Caekebeke J" first="Jo" last="Caekebeke">Jo Caekebeke</name></noRegion><name sortKey="Lu Bke, Ursula" sort="Lu Bke, Ursula" uniqKey="Lu Bke U" first="Ursula" last="Lu Bke">Ursula Lu Bke</name><name sortKey="Martin, Jean Jacques" sort="Martin, Jean Jacques" uniqKey="Martin J" first="Jean-Jacques" last="Martin">Jean-Jacques Martin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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