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Article: A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families

TitleA founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families
Authors
Issue Date2001
PublisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
Citation
Journal Of The American Medical Association, 2001, v. 286 n. 18, p. 2257-2263 How to Cite?
Abstract
Context Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites. Objective To identify variant alleles in genes related to familial early-onset AD among Caribbean Hispanics. Design and Setting Family-based case series conducted in 1998-2001 at an AD research center in New York, NY, and clinics in the Dominican Republic. Patients Among 206 Caribbean Hispanic families with 2 or more living members with AD who were identified, 19 (9.2%) had at least 1 individual with onset of AD before the age of 55 years. Main Outcome Measure The entire coding region of the presenilin 1 gene and exons 16 and 17 of the amyloid precursor protein gene were sequenced in probands from the 19 families and their living relatives. Results A G-to-C nucleotide change resulting in a glycine-alanine amino acid substitution at codon 206 (Gly206Ala) in exon 7 of presenilin 1 was observed in 23 individuals from 8 (42%) of the 19 families. A Caribbean Hispanic individual with the Gly206Ala mutation and early-onset familial disease was also found by sequencing the corresponding genes of 319 unrelated individuals in New York City. The Gly206Ala mutation was not found in public genetic databases but was reported in 5 individuals from 4 Hispanic families with AD referred for genetic testing. None of the members of these families were related to one another, yet all carriers of the Gly206Ala mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. No mutations were found in the amyloid precursor protein gene. Conclusions The Gly206Ala mutation was found in 8 of 19 unrelated Caribbean Hispanic families with early-onset familial AD. This genetic change may be a prevalent cause of early-onset familial AD in the Caribbean Hispanic population.
Persistent Identifierhttp://hdl.handle.net/10722/134758
ISSN
2013 Impact Factor: 30.387
ISI Accession Number ID
References

 

Author Affiliations
  1. Universidad Tecnologica de Santiago
  2. Columbia University in the City of New York
  3. University Health Network University of Toronto
  4. Gertrude H. Sergievsky Center
  5. Plaza de la Salud Hospital
  6. Athena Diagnostics, Inc.
  7. University of Toronto
  8. Columbia University, College of Physicians and Surgeons
DC FieldValueLanguage
dc.contributor.authorAthan, ESen_HK
dc.contributor.authorWilliamson, Jen_HK
dc.contributor.authorCiappa, Aen_HK
dc.contributor.authorSantana, Ven_HK
dc.contributor.authorRomas, SNen_HK
dc.contributor.authorLee, JHen_HK
dc.contributor.authorRondon, Hen_HK
dc.contributor.authorLantigua, RAen_HK
dc.contributor.authorMedrano, Men_HK
dc.contributor.authorTorres, Men_HK
dc.contributor.authorArawaka, Sen_HK
dc.contributor.authorRogaeva, Een_HK
dc.contributor.authorSong, YQen_HK
dc.contributor.authorSato, Cen_HK
dc.contributor.authorKawarai, Ten_HK
dc.contributor.authorFafel, KCen_HK
dc.contributor.authorBoss, MAen_HK
dc.contributor.authorSeltzer, WKen_HK
dc.contributor.authorStern, Yen_HK
dc.contributor.authorSt GeorgeHyslop, Pen_HK
dc.contributor.authorTycko, Ben_HK
dc.contributor.authorMayeux, Ren_HK
dc.date.accessioned2011-07-14T07:02:52Z-
dc.date.available2011-07-14T07:02:52Z-
dc.date.issued2001en_HK
dc.identifier.citationJournal Of The American Medical Association, 2001, v. 286 n. 18, p. 2257-2263en_HK
dc.identifier.issn0098-7484en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134758-
dc.description.abstractContext Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites. Objective To identify variant alleles in genes related to familial early-onset AD among Caribbean Hispanics. Design and Setting Family-based case series conducted in 1998-2001 at an AD research center in New York, NY, and clinics in the Dominican Republic. Patients Among 206 Caribbean Hispanic families with 2 or more living members with AD who were identified, 19 (9.2%) had at least 1 individual with onset of AD before the age of 55 years. Main Outcome Measure The entire coding region of the presenilin 1 gene and exons 16 and 17 of the amyloid precursor protein gene were sequenced in probands from the 19 families and their living relatives. Results A G-to-C nucleotide change resulting in a glycine-alanine amino acid substitution at codon 206 (Gly206Ala) in exon 7 of presenilin 1 was observed in 23 individuals from 8 (42%) of the 19 families. A Caribbean Hispanic individual with the Gly206Ala mutation and early-onset familial disease was also found by sequencing the corresponding genes of 319 unrelated individuals in New York City. The Gly206Ala mutation was not found in public genetic databases but was reported in 5 individuals from 4 Hispanic families with AD referred for genetic testing. None of the members of these families were related to one another, yet all carriers of the Gly206Ala mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. No mutations were found in the amyloid precursor protein gene. Conclusions The Gly206Ala mutation was found in 8 of 19 unrelated Caribbean Hispanic families with early-onset familial AD. This genetic change may be a prevalent cause of early-onset familial AD in the Caribbean Hispanic population.en_HK
dc.publisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtlen_HK
dc.relation.ispartofJournal of the American Medical Associationen_HK
dc.subject.meshAge of Onseten_US
dc.subject.meshAgeden_US
dc.subject.meshAlanineen_US
dc.subject.meshAlzheimer Disease/epidemiology/*geneticsen_US
dc.subject.meshAmyloid beta-Protein Precursor/geneticsen_US
dc.subject.meshApolipoproteins E/geneticsen_US
dc.subject.meshCaribbean Region/ethnologyen_US
dc.subject.meshDNA Mutational Analysisen_US
dc.subject.meshDominican Republic/ethnologyen_US
dc.subject.meshExonsen_US
dc.subject.meshGenotypeen_US
dc.subject.meshGlycineen_US
dc.subject.meshHaplotypesen_US
dc.subject.meshHispanic Americans/*geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshMembrane Proteins/*geneticsen_US
dc.subject.meshMicrosatellite Repeatsen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMutationen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshPolymorphism, Geneticen_US
dc.subject.meshPresenilin-1en_US
dc.subject.meshPuerto Rico/ethnologyen_US
dc.subject.meshUnited States/epidemiologyen_US
dc.titleA founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic familiesen_HK
dc.typeArticleen_HK
dc.identifier.emailSong, YQ:songy@hkucc.hku.hken_HK
dc.identifier.authoritySong, YQ=rp00488en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid11710891en_HK
dc.identifier.scopuseid_2-s2.0-0035860986en_HK
dc.identifier.hkuros69634-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035860986&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume286en_HK
dc.identifier.issue18en_HK
dc.identifier.spage2257en_HK
dc.identifier.epage2263en_HK
dc.identifier.isiWOS:000172129700020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridAthan, ES=6701602227en_HK
dc.identifier.scopusauthoridWilliamson, J=7403200164en_HK
dc.identifier.scopusauthoridCiappa, A=6602684794en_HK
dc.identifier.scopusauthoridSantana, V=7005537193en_HK
dc.identifier.scopusauthoridRomas, SN=6603418447en_HK
dc.identifier.scopusauthoridLee, JH=16319281700en_HK
dc.identifier.scopusauthoridRondon, H=6506606186en_HK
dc.identifier.scopusauthoridLantigua, RA=7003355284en_HK
dc.identifier.scopusauthoridMedrano, M=7006746251en_HK
dc.identifier.scopusauthoridTorres, M=7402581470en_HK
dc.identifier.scopusauthoridArawaka, S=6602984633en_HK
dc.identifier.scopusauthoridRogaeva, E=35372614800en_HK
dc.identifier.scopusauthoridSong, YQ=7404921212en_HK
dc.identifier.scopusauthoridSato, C=7201887342en_HK
dc.identifier.scopusauthoridKawarai, T=7003632751en_HK
dc.identifier.scopusauthoridFafel, KC=6508131866en_HK
dc.identifier.scopusauthoridBoss, MA=7006259285en_HK
dc.identifier.scopusauthoridSeltzer, WK=7004205766en_HK
dc.identifier.scopusauthoridStern, Y=7103273845en_HK
dc.identifier.scopusauthoridSt GeorgeHyslop, P=7005637468en_HK
dc.identifier.scopusauthoridTycko, B=7006946546en_HK
dc.identifier.scopusauthoridMayeux, R=7101793222en_HK

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