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
Ciappa, A8
Santana, V8
Romas, SN8
Lee, JH2 8
Rondon, H5
Lantigua, RA8
Medrano, M1
Torres, M5
Arawaka, S3 7
Rogaeva, E3 7
Song, YQ3 7
Sato, C3 7
Kawarai, T3 7
Fafel, KC6
Boss, MA6
Seltzer, WK6
Stern, Y8
St GeorgeHyslop, P3 7
Tycko, B8
Mayeux, R2 4 8
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
2011 Impact Factor: 30.026
2011 SCImago Journal Rankings: 1.579
ISI Accession Number IDWOS:000172129700020
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 30.026
2011 SCImago Journal Rankings: 1.579
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
Author Affiliations
  1. Universidad Tecnologica de Santiago
  2. Columbia University in the City of New York
  3. University Health Network
  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