Article: Screening for PS1 mutations in a referral-based series of AD cases: 21 Novel mutations

File Download
  • No File Attached
Links for fulltext
(May Require Subscription)
Supplementary
  • Basic View
  • Metadata View
  • XML View
TitleScreening for PS1 mutations in a referral-based series of AD cases: 21 Novel mutations
AuthorsRogaeva, EA3
Fafel, KC4
Song, YQ3
Medeiros, H3
Sato, C3
Liang, Y3
Richard, E3
Rogaev, EI2 3
Frommelt, P5
Sadovnick, AD6
Meschino, W7
Rockwood, K8
Boss, MA4
Mayeux, R1
St GeorgeHyslop, P3
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
2011 Impact Factor: 8.312
2011 SCImago Journal Rankings: 0.534
ISI Accession Number IDWOS:000170623900009
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 8.312
2011 SCImago Journal Rankings: 0.534
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
Author Affiliations
  1. null
  2. Russian Academy of Medical Sciences
  3. University Health Network
  4. Athena Diagnostics, Inc.
  5. Asklepios Klinik Schaufling
  6. The University of British Columbia
  7. North York General Hospital
  8. Dalhousie University