APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy
Identifieur interne : 001596 ( Main/Exploration ); précédent : 001595; suivant : 001597APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy
Auteurs : Kristel Sleegers [Belgique] ; Nathalie Brouwers [Belgique] ; Ilse Gijselinck [Belgique] ; Jessie Theuns [Belgique] ; Dirk Goossens [Belgique] ; Jan Wauters [Belgique] ; Jurgen Del-Favero [Belgique] ; Marc Cruts [Belgique] ; Cornelia M. Van Duijn [Pays-Bas] ; Christine Van Broeckhoven [Belgique]Source :
- Brain [ 0006-8950 ] ; 2006-08-18.
Abstract
We assessed the impact of amyloid precursor protein (APP) gene locus duplications in early onset Alzheimer's disease in a Dutch population-based sample. Using real-time PCR and an in-house-developed multiplex amplicon quantification assay, we identified a genomic APP duplication in 1 out of 10 multigenerational families segregating early onset Alzheimer's disease. In this family, cerebral amyloid angiopathy (CAA) coincided with this disease. The duplicated genomic region included no other genes than APP and extended maximally over 0.7 Mb. In a sample of 65 familial early onset patients, we observed the same APP genomic duplication in one patient (1.7%), while in 36 isolated patients duplications in the APP locus were absent. This indicated that APP locus duplications explained <2% of familial, non-autosomal dominant Alzheimer's disease and are an infrequent cause of de novo mutation. Our findings corroborated a recent French study, and indicated that investigating genomic duplications in the APP locus in families segregating Alzheimer's disease and CAA should be considered.
Url:
DOI: 10.1093/brain/awl203
Affiliations:
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Van Duijn</name></author><author><name sortKey="Broeckhoven, Christine Van" sort="Broeckhoven, Christine Van" uniqKey="Broeckhoven C" first="Christine Van" last="Broeckhoven">Christine Van Broeckhoven</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B49F788AB3EE951B27E7BC426F76BA7CD5DAFA3D</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1093/brain/awl203</idno><idno type="url">https://api.istex.fr/document/B49F788AB3EE951B27E7BC426F76BA7CD5DAFA3D/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000566</idno><idno type="wicri:Area/Istex/Curation">000566</idno><idno type="wicri:Area/Istex/Checkpoint">001042</idno><idno type="wicri:doubleKey">0006-8950:2006:Sleegers K:app:duplication:is</idno><idno type="wicri:Area/Main/Merge">001604</idno><idno type="wicri:Area/Main/Curation">001596</idno><idno type="wicri:Area/Main/Exploration">001596</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy</title><author><name sortKey="Sleegers, Kristel" sort="Sleegers, Kristel" uniqKey="Sleegers K" first="Kristel" last="Sleegers">Kristel Sleegers</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Brouwers, Nathalie" sort="Brouwers, Nathalie" uniqKey="Brouwers N" first="Nathalie" last="Brouwers">Nathalie Brouwers</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Gijselinck, Ilse" sort="Gijselinck, Ilse" uniqKey="Gijselinck I" first="Ilse" last="Gijselinck">Ilse Gijselinck</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Goossens, Dirk" sort="Goossens, Dirk" uniqKey="Goossens D" first="Dirk" last="Goossens">Dirk Goossens</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, University of Antwerp Antwerp</wicri:regionArea><wicri:noRegion>University of Antwerp Antwerp</wicri:noRegion></affiliation></author><author><name sortKey="Wauters, Jan" sort="Wauters, Jan" uniqKey="Wauters J" first="Jan" last="Wauters">Jan Wauters</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Center of Medical Genetics, University Hospital Antwerp Antwerp</wicri:regionArea><wicri:noRegion>University Hospital Antwerp Antwerp</wicri:noRegion></affiliation></author><author><name sortKey="Del Favero, Jurgen" sort="Del Favero, Jurgen" uniqKey="Del Favero J" first="Jurgen" last="Del-Favero">Jurgen Del-Favero</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, University of Antwerp Antwerp</wicri:regionArea><wicri:noRegion>University of Antwerp Antwerp</wicri:noRegion></affiliation></author><author><name sortKey="Cruts, Marc" sort="Cruts, Marc" uniqKey="Cruts M" first="Marc" last="Cruts">Marc Cruts</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group Antwerp</wicri:regionArea></affiliation></author><author><name sortKey="Duijn, Cornelia M Van" sort="Duijn, Cornelia M Van" uniqKey="Duijn C" first="Cornelia M. Van" last="Duijn">Cornelia M. Van Duijn</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics Erasmus MC, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Broeckhoven, Christine Van" sort="Broeckhoven, Christine Van" uniqKey="Broeckhoven C" first="Christine Van" last="Broeckhoven">Christine Van Broeckhoven</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group Antwerp</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2006-08-18">2006-08-18</date><biblScope unit="volume">129</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="2977">2977</biblScope><biblScope unit="page" to="2983">2983</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">B49F788AB3EE951B27E7BC426F76BA7CD5DAFA3D</idno><idno type="DOI">10.1093/brain/awl203</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">We assessed the impact of amyloid precursor protein (APP) gene locus duplications in early onset Alzheimer's disease in a Dutch population-based sample. Using real-time PCR and an in-house-developed multiplex amplicon quantification assay, we identified a genomic APP duplication in 1 out of 10 multigenerational families segregating early onset Alzheimer's disease. In this family, cerebral amyloid angiopathy (CAA) coincided with this disease. The duplicated genomic region included no other genes than APP and extended maximally over 0.7 Mb. In a sample of 65 familial early onset patients, we observed the same APP genomic duplication in one patient (1.7%), while in 36 isolated patients duplications in the APP locus were absent. This indicated that APP locus duplications explained <2% of familial, non-autosomal dominant Alzheimer's disease and are an infrequent cause of de novo mutation. Our findings corroborated a recent French study, and indicated that investigating genomic duplications in the APP locus in families segregating Alzheimer's disease and CAA should be considered.</div></front></TEI><affiliations><list><country><li>Belgique</li><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li></region><settlement><li>Rotterdam</li></settlement></list><tree><country name="Belgique"><noRegion><name sortKey="Sleegers, Kristel" sort="Sleegers, Kristel" uniqKey="Sleegers K" first="Kristel" last="Sleegers">Kristel Sleegers</name></noRegion><name sortKey="Broeckhoven, Christine Van" sort="Broeckhoven, Christine Van" uniqKey="Broeckhoven C" first="Christine Van" last="Broeckhoven">Christine Van Broeckhoven</name><name sortKey="Brouwers, Nathalie" sort="Brouwers, Nathalie" uniqKey="Brouwers N" first="Nathalie" last="Brouwers">Nathalie Brouwers</name><name sortKey="Cruts, Marc" sort="Cruts, Marc" uniqKey="Cruts M" first="Marc" last="Cruts">Marc Cruts</name><name sortKey="Del Favero, Jurgen" sort="Del Favero, Jurgen" uniqKey="Del Favero J" first="Jurgen" last="Del-Favero">Jurgen Del-Favero</name><name sortKey="Gijselinck, Ilse" sort="Gijselinck, Ilse" uniqKey="Gijselinck I" first="Ilse" last="Gijselinck">Ilse Gijselinck</name><name sortKey="Goossens, Dirk" sort="Goossens, Dirk" uniqKey="Goossens D" first="Dirk" last="Goossens">Dirk Goossens</name><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name><name sortKey="Wauters, Jan" sort="Wauters, Jan" uniqKey="Wauters J" first="Jan" last="Wauters">Jan Wauters</name></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Duijn, Cornelia M Van" sort="Duijn, Cornelia M Van" uniqKey="Duijn C" first="Cornelia M. Van" last="Duijn">Cornelia M. Van Duijn</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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