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dc.contributor.authorBiffi, Alessandro
dc.contributor.authorPlourde, Anna
dc.contributor.authorShen, Yiping
dc.contributor.authorOnofrio, Robert
dc.contributor.authorSmith, Eric E.
dc.contributor.authorFrosch, Matthew P.
dc.contributor.authorPrada, Claudia M.
dc.contributor.authorGusella, James Francis
dc.contributor.authorGreenberg, Steven Mark
dc.contributor.authorRosand, Jonathan
dc.date.accessioned2011-04-29T02:02:00Z
dc.date.issued2010
dc.identifier.citationBiffi, Alessandro, Anna Plourde, Yiping Shen, Robert Onofrio, Eric E. Smith, Matthew Frosch, Claudia M. Prada, James Gusella, Steven M. Greenberg, and Jonathan Rosand. 2010. Screening for Familial APP Mutations in Sporadic Cerebral Amyloid Angiopathy. PLoS ONE 5(11): e13949.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4879200
dc.description.abstractBackground: Advances in genetic technology have revealed that variation in the same gene can cause both rare familial and common sporadic forms of the same disease. Cerebral amyloid angiopathy (CAA), a common cause of symptomatic intracerebral hemorrhage (ICH) in the elderly, can also occur in families in an autosomal dominant pattern. The majority of affected families harbor mutations in the Beta amyloid Peptide (Aβ) coding region of the gene for amyloid precursor protein (APP) or have duplications of chromosomal segments containing APP. Methodology/Principal Findings: A total of 58 subjects with a diagnosis of probable or definite CAA according to validated criteria were included in the present study. We sequenced the Aβ coding region of APP in 58 individuals and performed multiplex ligation-dependent probe amplification to determine APP gene dosage in 60. No patient harbored a known or novel APP mutation or gene duplication. The frequency of mutations investigated in the present study is estimated to range from 0% to 8% in individuals with probable CAA in the general population, based on the ascertained sample size. Conclusions/Significance: We found no evidence that variants at loci associated with familial CAA play a role in sporadic CAA. Based on our findings, these rare highly-penetrant mutations are unlikely to be seen in sporadic CAA patients. Therefore, our results do not support systematic genetic screening of CAA patients who lack a strong family history of hemorrhage or dementia.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0013949en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978718/pdf/en_US
dash.licenseLAA
dc.subjectgenetics and genomicsen_US
dc.subjectcomplex traitsen_US
dc.subjectgenetics of diseaseen_US
dc.subjectneurological disordersen_US
dc.subjectcerebrovascular diseaseen_US
dc.subjectneurogeneticsen_US
dc.titleScreening for Familial APP Mutations in Sporadic Cerebral Amyloid Angiopathyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorGusella, James Francis
dc.date.available2011-04-29T02:02:00Z
dash.affiliation.otherHMS^Geneticsen_US
dc.identifier.doi10.1371/journal.pone.0013949*
dash.contributor.affiliatedRosand, Jonathan
dash.contributor.affiliatedGusella, James
dash.contributor.affiliatedBiffi, Alessandro
dash.contributor.affiliatedShen, Yiping
dash.contributor.affiliatedGreenberg, Steven
dash.contributor.affiliatedFrosch, Matthew


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