Segregation analysis of Alzheimer pedigrees: rare Mendelian dominant mutation(s) explain a minority of early-onset cases. French Alzheimer Collaborative Group.
Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ( < or = age 60 years) AD (EOAD) probands has been carried out, allowing for a mixture in AD inheritance among probands. The goal was to quantify the proportion of probands that could be explained by autosomal inheritance of a rare disease allele "a" at a Mendelian dominant gene (MDG). Our data provide strong evidence for a mixture of two distributions; AD transmission is fully explained by MDG inheritance in < 20% of probands. Male and female age-of-onset distributions are significantly different for "AA" but not for "aA" subjects. For "aA" subjects the estimated penetrance value was close to 1 by age 60. For "AA" subjects, it reaches, by age 90, 10% (males) and 30% (females). We show a clear cutoff in the posterior probability of being an MDG case.
Martinez
M
M
INSERM U-155, Paris, France.
Campion
D
D
Babron
M C
MC
Hannequin
D
D
Agid
Y
Y
Bellis
M
M
Brice
A
A
Mallet
J
J
Michon
A
A
Thomas-Anterion
C
C
Clerget-Darpoux
F
F
D000367:Age Factors; D017668:Age of Onset; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008432:Mathematical Computing; D009154:Mutation; D010375:Pedigree; D012307:Risk Factors; D012737:Sex Factors