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Article: A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families
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TitleA founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families
 
AuthorsAthan, ES8
Williamson, J8 8
Ciappa, A8
Santana, V8 8
Romas, SN8 8
Lee, JH8 8 2
Rondon, H5
Lantigua, RA8 8
Medrano, M1
Torres, M5
Arawaka, S7 3
Rogaeva, E7 3
Song, YQ7 3
Sato, C7 3
Kawarai, T7 3
Fafel, KC6
Boss, MA6
Seltzer, WK6
Stern, Y8 8 8 8
St GeorgeHyslop, P7 3
Tycko, B8 8
Mayeux, R8 8 8 8 2 4
 
Issue Date2001
 
PublisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
 
CitationJournal Of The American Medical Association, 2001, v. 286 n. 18, p. 2257-2263 [How to Cite?]
 
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.
 
ISSN0098-7484
2012 Impact Factor: 29.978
2012 SCImago Journal Rankings: 4.843
 
ISI Accession Number IDWOS:000172129700020
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorAthan, ES
 
dc.contributor.authorWilliamson, J
 
dc.contributor.authorCiappa, A
 
dc.contributor.authorSantana, V
 
dc.contributor.authorRomas, SN
 
dc.contributor.authorLee, JH
 
dc.contributor.authorRondon, H
 
dc.contributor.authorLantigua, RA
 
dc.contributor.authorMedrano, M
 
dc.contributor.authorTorres, M
 
dc.contributor.authorArawaka, S
 
dc.contributor.authorRogaeva, E
 
dc.contributor.authorSong, YQ
 
dc.contributor.authorSato, C
 
dc.contributor.authorKawarai, T
 
dc.contributor.authorFafel, KC
 
dc.contributor.authorBoss, MA
 
dc.contributor.authorSeltzer, WK
 
dc.contributor.authorStern, Y
 
dc.contributor.authorSt GeorgeHyslop, P
 
dc.contributor.authorTycko, B
 
dc.contributor.authorMayeux, R
 
dc.date.accessioned2011-07-14T07:02:52Z
 
dc.date.available2011-07-14T07:02:52Z
 
dc.date.issued2001
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of The American Medical Association, 2001, v. 286 n. 18, p. 2257-2263 [How to Cite?]
 
dc.identifier.epage2263
 
dc.identifier.hkuros69634
 
dc.identifier.isiWOS:000172129700020
 
dc.identifier.issn0098-7484
2012 Impact Factor: 29.978
2012 SCImago Journal Rankings: 4.843
 
dc.identifier.issue18
 
dc.identifier.pmid11710891
 
dc.identifier.scopuseid_2-s2.0-0035860986
 
dc.identifier.spage2257
 
dc.identifier.urihttp://hdl.handle.net/10722/134758
 
dc.identifier.volume286
 
dc.publisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of the American Medical Association
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAge of Onset
 
dc.subject.meshAged
 
dc.subject.meshAlanine
 
dc.subject.meshAlzheimer Disease/epidemiology/*genetics
 
dc.subject.meshAmyloid beta-Protein Precursor/genetics
 
dc.subject.meshApolipoproteins E/genetics
 
dc.subject.meshCaribbean Region/ethnology
 
dc.subject.meshDNA Mutational Analysis
 
dc.subject.meshDominican Republic/ethnology
 
dc.subject.meshExons
 
dc.subject.meshGenotype
 
dc.subject.meshGlycine
 
dc.subject.meshHaplotypes
 
dc.subject.meshHispanic Americans/*genetics
 
dc.subject.meshHumans
 
dc.subject.meshMembrane Proteins/*genetics
 
dc.subject.meshMicrosatellite Repeats
 
dc.subject.meshMiddle Aged
 
dc.subject.meshMutation
 
dc.subject.meshPhenotype
 
dc.subject.meshPolymorphism, Genetic
 
dc.subject.meshPresenilin-1
 
dc.subject.meshPuerto Rico/ethnology
 
dc.subject.meshUnited States/epidemiology
 
dc.titleA founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families
 
dc.typeArticle
 
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<item><contributor.author>Athan, ES</contributor.author>
<contributor.author>Williamson, J</contributor.author>
<contributor.author>Ciappa, A</contributor.author>
<contributor.author>Santana, V</contributor.author>
<contributor.author>Romas, SN</contributor.author>
<contributor.author>Lee, JH</contributor.author>
<contributor.author>Rondon, H</contributor.author>
<contributor.author>Lantigua, RA</contributor.author>
<contributor.author>Medrano, M</contributor.author>
<contributor.author>Torres, M</contributor.author>
<contributor.author>Arawaka, S</contributor.author>
<contributor.author>Rogaeva, E</contributor.author>
<contributor.author>Song, YQ</contributor.author>
<contributor.author>Sato, C</contributor.author>
<contributor.author>Kawarai, T</contributor.author>
<contributor.author>Fafel, KC</contributor.author>
<contributor.author>Boss, MA</contributor.author>
<contributor.author>Seltzer, WK</contributor.author>
<contributor.author>Stern, Y</contributor.author>
<contributor.author>St GeorgeHyslop, P</contributor.author>
<contributor.author>Tycko, B</contributor.author>
<contributor.author>Mayeux, R</contributor.author>
<date.accessioned>2011-07-14T07:02:52Z</date.accessioned>
<date.available>2011-07-14T07:02:52Z</date.available>
<date.issued>2001</date.issued>
<identifier.citation>Journal Of The American Medical Association, 2001, v. 286 n. 18, p. 2257-2263</identifier.citation>
<identifier.issn>0098-7484</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/134758</identifier.uri>
<description.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.</description.abstract>
<publisher>American Medical Association. The Journal&apos;s web site is located at http://jama.ama-assn.org/index.dtl</publisher>
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<subject.mesh>Age of Onset</subject.mesh>
<subject.mesh>Aged</subject.mesh>
<subject.mesh>Alanine</subject.mesh>
<subject.mesh>Alzheimer Disease/epidemiology/*genetics</subject.mesh>
<subject.mesh>Amyloid beta-Protein Precursor/genetics</subject.mesh>
<subject.mesh>Apolipoproteins E/genetics</subject.mesh>
<subject.mesh>Caribbean Region/ethnology</subject.mesh>
<subject.mesh>DNA Mutational Analysis</subject.mesh>
<subject.mesh>Dominican Republic/ethnology</subject.mesh>
<subject.mesh>Exons</subject.mesh>
<subject.mesh>Genotype</subject.mesh>
<subject.mesh>Glycine</subject.mesh>
<subject.mesh>Haplotypes</subject.mesh>
<subject.mesh>Hispanic Americans/*genetics</subject.mesh>
<subject.mesh>Humans</subject.mesh>
<subject.mesh>Membrane Proteins/*genetics</subject.mesh>
<subject.mesh>Microsatellite Repeats</subject.mesh>
<subject.mesh>Middle Aged</subject.mesh>
<subject.mesh>Mutation</subject.mesh>
<subject.mesh>Phenotype</subject.mesh>
<subject.mesh>Polymorphism, Genetic</subject.mesh>
<subject.mesh>Presenilin-1</subject.mesh>
<subject.mesh>Puerto Rico/ethnology</subject.mesh>
<subject.mesh>United States/epidemiology</subject.mesh>
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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