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dc.contributor.authorNicolas, Gaëlen
dc.contributor.authorAcuña-Hidalgo, Rocíoen
dc.contributor.authorKeogh, Michael Jen
dc.contributor.authorQuenez, Olivieren
dc.contributor.authorSteehouwer, Marloesen
dc.contributor.authorLelieveld, Stefanen
dc.contributor.authorRousseau, Stéphaneen
dc.contributor.authorRichard, Anne-Claireen
dc.contributor.authorOud, Manon Sen
dc.contributor.authorMarguet, Florenten
dc.contributor.authorLaquerrière, Annieen
dc.contributor.authorMorris, Chris Men
dc.contributor.authorAttems, Johannesen
dc.contributor.authorSmith, Colinen
dc.contributor.authorAnsorge, Olafen
dc.contributor.authorAl Sarraj, Safaen
dc.contributor.authorFrebourg, Thierryen
dc.contributor.authorCampion, Dominiqueen
dc.contributor.authorHannequin, Didieren
dc.contributor.authorWallon, Daviden
dc.contributor.authorGilissen, Christianen
dc.contributor.authorChinnery, Patricken
dc.contributor.authorVeltman, Joris Aen
dc.contributor.authorHoischen, Alexanderen
dc.date.accessioned2018-10-03T04:46:02Z
dc.date.available2018-10-03T04:46:02Z
dc.date.issued2018-12en
dc.identifier.issn1552-5260
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283114
dc.description.abstractINTRODUCTION. A minority of patients with sporadic early-onset Alzheimer disease (AD) exhibit de novo germline mutations in the autosomal dominant genes APP, PSEN1, or PSEN2. We hypothesized that negatively-screened patients may harbor somatic variants in these genes. METHODS. We applied an ultra-sensitive approach based on single-molecule molecular inversion probes followed by deep next generation sequencing of 11 genes to 100 brain and 355 blood samples from 445 sporadic AD patients (>80% exhibited an early onset, <66 years). RESULTS. We identified and confirmed by independent amplicon-based deep sequencing 9 somatic variants (allele fractions: 0.2%-10.8%): two APP, five SORL1, one NCSTN and one MARK4 variant. DISCUSSION. Two of the SORL1 variants might have contributed to the disease, the two APP variants were interpreted as likely benign and the other variants remained of unknown significance. Somatic variants in the autosomal dominant AD genes may not be a common cause of sporadic AD, including early onset cases.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectHumansen
dc.subjectAlzheimer Diseaseen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGenes, Dominanten
dc.subjectMutationen
dc.subjectAdulten
dc.subjectAgeden
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectMaleen
dc.titleSomatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer's disease.en
dc.typeArticle
prism.endingPage1639
prism.issueIdentifier12en
prism.publicationDate2018en
prism.publicationNameAlzheimer's & dementia : the journal of the Alzheimer's Associationen
prism.startingPage1632
prism.volume14en
dc.identifier.doi10.17863/CAM.30475
dcterms.dateAccepted2018-06-15en
rioxxterms.versionofrecord10.1016/j.jalz.2018.06.3056en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-12en
dc.contributor.orcidNicolas, Gaël [0000-0001-9391-7800]
dc.contributor.orcidOud, Manon S [0000-0001-9513-3030]
dc.contributor.orcidMorris, Chris M [0000-0002-3749-0993]
dc.contributor.orcidAttems, Johannes [0000-0003-1636-1700]
dc.contributor.orcidChinnery, Patrick [0000-0002-7065-6617]
dc.contributor.orcidVeltman, Joris A [0000-0002-3218-8250]
dc.identifier.eissn1552-5279
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (103396/A/13/Z)
pubs.funder-project-idMRC (via University of Edinburgh) (162126)
pubs.funder-project-idWELLCOME TRUST (101876/Z/13/Z)


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International