PMID- 10441572
OWN - NLM
STAT- MEDLINE
DCOM- 19991004
LR  - 20220409
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 3
DP  - 1999 Sep
TI  - Early-onset autosomal dominant Alzheimer disease: prevalence, genetic
      heterogeneity, and mutation spectrum.
PG  - 664-70
AB  - To determine the prevalence of early-onset Alzheimer disease (EOAD) and of
      autosomal dominant forms of EOAD (ADEOAD), we performed a population-based study 
      in the city of Rouen (426,710 residents). EOAD was defined as onset of disease at
      age <61 years, and ADEOAD was defined as the occurrence of at least three EOAD
      cases in three generations. Using these stringent criteria, we calculated that
      the EOAD and ADEOAD prevalences per 100,000 persons at risk were 41.2 and 5.3,
      respectively. We then performed a mutational analysis of the genes for amyloid
      precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) in 34
      families with ADEOAD ascertained in France. In 19 (56%) of these families, we
      identified 16 distinct PSEN1 missense mutations, including 4 (Thr147Ile,
      Trp165Cys, Leu173Trp, and Ser390Ile) not reported elsewhere. APP mutations,
      including a novel mutation located at codon 715, were identified in 5 (15%) of
      the families. In the 10 remaining ADEOAD families and in 9 additional autosomal
      dominant Alzheimer disease families that did not fulfill the strict criteria for 
      ADEOAD, no PSEN1, PSEN2, or APP mutation was identified. These results show that 
      (1) PSEN1 and APP mutations account for 71% of ADEOAD families and (2)
      nonpenetrance at age <61 years is probably infrequent for PSEN1 or APP mutations.
FAU - Campion, D
AU  - Campion D
AD  - INSERM EPI 9906, Faculte de Medecine, 76183 Rouen, France.
FAU - Dumanchin, C
AU  - Dumanchin C
FAU - Hannequin, D
AU  - Hannequin D
FAU - Dubois, B
AU  - Dubois B
FAU - Belliard, S
AU  - Belliard S
FAU - Puel, M
AU  - Puel M
FAU - Thomas-Anterion, C
AU  - Thomas-Anterion C
FAU - Michon, A
AU  - Michon A
FAU - Martin, C
AU  - Martin C
FAU - Charbonnier, F
AU  - Charbonnier F
FAU - Raux, G
AU  - Raux G
FAU - Camuzat, A
AU  - Camuzat A
FAU - Penet, C
AU  - Penet C
FAU - Mesnage, V
AU  - Mesnage V
FAU - Martinez, M
AU  - Martinez M
FAU - Clerget-Darpoux, F
AU  - Clerget-Darpoux F
FAU - Brice, A
AU  - Brice A
FAU - Frebourg, T
AU  - Frebourg T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Codon)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (PSEN2 protein, human)
RN  - 0 (Presenilin-1)
RN  - 0 (Presenilin-2)
SB  - IM
MH  - Adult
MH  - *Age of Onset
MH  - Aged
MH  - Alzheimer Disease/diagnosis/*epidemiology/*genetics
MH  - Amino Acid Substitution
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Codon/genetics
MH  - DNA Mutational Analysis
MH  - Exons/genetics
MH  - Female
MH  - France/epidemiology
MH  - Gene Frequency
MH  - *Genes, Dominant
MH  - *Genetic Heterogeneity
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Pedigree
MH  - Penetrance
MH  - Presenilin-1
MH  - Presenilin-2
MH  - Prevalence
PMC - PMC1377972
EDAT- 1999/08/12 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/08/12 10:00
PHST- 1999/08/12 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/08/12 10:00 [entrez]
AID - S0002-9297(07)62317-9 [pii]
AID - 10.1086/302553 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Sep;65(3):664-70. doi: 10.1086/302553.