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Article: Screening for PS1 mutations in a referral-based series of AD cases: 21 Novel mutations
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TitleScreening for PS1 mutations in a referral-based series of AD cases: 21 Novel mutations
 
AuthorsRogaeva, EA2
Fafel, KC4
Song, YQ2
Medeiros, H2
Sato, C2
Liang, Y2
Richard, E2
Rogaev, EI2 3
Frommelt, P6
Sadovnick, AD5
Meschino, W7
Rockwood, K8
Boss, MA4
Mayeux, R1
St GeorgeHyslop, P2
 
Issue Date2001
 
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurology.org
 
CitationNeurology, 2001, v. 57 n. 4, p. 621-625 [How to Cite?]
 
AbstractBackground: Mutations in the presenilin-1 gene (PS1) account for a majority of patients with early onset familial AD. However, the clinical indications and algorithms for genetic testing in dementia are still evolving. Methods: The entire open reading frame of the PS1 gene was sequenced in a series of 414 consecutive patients referred for diagnostic testing, including 372 patients with AD and 42 asymptomatic persons with a strong family history of AD. Results: Forty-eight independent patients screened had a PS1 mutation including 21 novel mutations. In addition, 3% of subjects (11/413) had a known polymorphism, the Glu318Gly substitution. The majority of the mutations were missense substitutions but there were three insertions and Δexon 10 mutation. With six exceptions (codons 35, 178, 352, 354, 358, and 365) most of the mutations occurred at residues conserved in the homologous PS2 gene or in PS1 of other species. Conclusions: Eleven percent of a referral-based series of patients with AD can be explained by coding sequence mutations in the PS1 gene. The high frequency of PS1 mutations in this study indicates that screening for PS1 mutations in AD is likely to be successful, especially when directed at patients with a positive family history with onset before 60 years (90% of those with PS1 mutations were affected by age 60 years). This will also have significance for the secondary identification of at-risk relatives who might be candidates for future prophylactic therapies for AD.
 
ISSN0028-3878
2013 Impact Factor: 8.303
 
ISI Accession Number IDWOS:000170623900009
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorRogaeva, EA
 
dc.contributor.authorFafel, KC
 
dc.contributor.authorSong, YQ
 
dc.contributor.authorMedeiros, H
 
dc.contributor.authorSato, C
 
dc.contributor.authorLiang, Y
 
dc.contributor.authorRichard, E
 
dc.contributor.authorRogaev, EI
 
dc.contributor.authorFrommelt, P
 
dc.contributor.authorSadovnick, AD
 
dc.contributor.authorMeschino, W
 
dc.contributor.authorRockwood, K
 
dc.contributor.authorBoss, MA
 
dc.contributor.authorMayeux, R
 
dc.contributor.authorSt GeorgeHyslop, P
 
dc.date.accessioned2011-07-14T07:02:29Z
 
dc.date.available2011-07-14T07:02:29Z
 
dc.date.issued2001
 
dc.description.abstractBackground: Mutations in the presenilin-1 gene (PS1) account for a majority of patients with early onset familial AD. However, the clinical indications and algorithms for genetic testing in dementia are still evolving. Methods: The entire open reading frame of the PS1 gene was sequenced in a series of 414 consecutive patients referred for diagnostic testing, including 372 patients with AD and 42 asymptomatic persons with a strong family history of AD. Results: Forty-eight independent patients screened had a PS1 mutation including 21 novel mutations. In addition, 3% of subjects (11/413) had a known polymorphism, the Glu318Gly substitution. The majority of the mutations were missense substitutions but there were three insertions and Δexon 10 mutation. With six exceptions (codons 35, 178, 352, 354, 358, and 365) most of the mutations occurred at residues conserved in the homologous PS2 gene or in PS1 of other species. Conclusions: Eleven percent of a referral-based series of patients with AD can be explained by coding sequence mutations in the PS1 gene. The high frequency of PS1 mutations in this study indicates that screening for PS1 mutations in AD is likely to be successful, especially when directed at patients with a positive family history with onset before 60 years (90% of those with PS1 mutations were affected by age 60 years). This will also have significance for the secondary identification of at-risk relatives who might be candidates for future prophylactic therapies for AD.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationNeurology, 2001, v. 57 n. 4, p. 621-625 [How to Cite?]
 
dc.identifier.epage625
 
dc.identifier.isiWOS:000170623900009
 
dc.identifier.issn0028-3878
2013 Impact Factor: 8.303
 
dc.identifier.issue4
 
dc.identifier.pmid11524469
 
dc.identifier.scopuseid_2-s2.0-0035964209
 
dc.identifier.spage621
 
dc.identifier.urihttp://hdl.handle.net/10722/134745
 
dc.identifier.volume57
 
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurology.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofNeurology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdult
 
dc.subject.meshAged
 
dc.subject.meshAged, 80 and over
 
dc.subject.meshAlzheimer Disease/diagnosis/*genetics
 
dc.subject.meshGenetic Testing/*methods
 
dc.subject.meshHumans
 
dc.subject.meshMembrane Proteins/*genetics
 
dc.subject.meshMiddle Aged
 
dc.subject.meshMutation/*genetics
 
dc.subject.meshPresenilin-1
 
dc.subject.meshReferral and Consultation
 
dc.subject.meshSurvival Analysis
 
dc.titleScreening for PS1 mutations in a referral-based series of AD cases: 21 Novel mutations
 
dc.typeArticle
 
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<contributor.author>Song, YQ</contributor.author>
<contributor.author>Medeiros, H</contributor.author>
<contributor.author>Sato, C</contributor.author>
<contributor.author>Liang, Y</contributor.author>
<contributor.author>Richard, E</contributor.author>
<contributor.author>Rogaev, EI</contributor.author>
<contributor.author>Frommelt, P</contributor.author>
<contributor.author>Sadovnick, AD</contributor.author>
<contributor.author>Meschino, W</contributor.author>
<contributor.author>Rockwood, K</contributor.author>
<contributor.author>Boss, MA</contributor.author>
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<contributor.author>St GeorgeHyslop, P</contributor.author>
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<description.abstract>Background: Mutations in the presenilin-1 gene (PS1) account for a majority of patients with early onset familial AD. However, the clinical indications and algorithms for genetic testing in dementia are still evolving. Methods: The entire open reading frame of the PS1 gene was sequenced in a series of 414 consecutive patients referred for diagnostic testing, including 372 patients with AD and 42 asymptomatic persons with a strong family history of AD. Results: Forty-eight independent patients screened had a PS1 mutation including 21 novel mutations. In addition, 3% of subjects (11/413) had a known polymorphism, the Glu318Gly substitution. The majority of the mutations were missense substitutions but there were three insertions and &#916;exon 10 mutation. With six exceptions (codons 35, 178, 352, 354, 358, and 365) most of the mutations occurred at residues conserved in the homologous PS2 gene or in PS1 of other species. Conclusions: Eleven percent of a referral-based series of patients with AD can be explained by coding sequence mutations in the PS1 gene. The high frequency of PS1 mutations in this study indicates that screening for PS1 mutations in AD is likely to be successful, especially when directed at patients with a positive family history with onset before 60 years (90% of those with PS1 mutations were affected by age 60 years). This will also have significance for the secondary identification of at-risk relatives who might be candidates for future prophylactic therapies for AD.</description.abstract>
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<subject.mesh>Aged</subject.mesh>
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<subject.mesh>Membrane Proteins/*genetics</subject.mesh>
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Author Affiliations
  1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain
  2. University Health Network University of Toronto
  3. Russian Academy of Medical Sciences
  4. Athena Diagnostics, Inc.
  5. The University of British Columbia
  6. Asklepios Klinik Schaufling
  7. North York General Hospital
  8. Dalhousie University