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Title: Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases

Abstract

Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ({le}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 {open_quotes}a{close_quotes} 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 {open_quotes}AA{close_quote} but not for {open_quotes}aA{close_quote} subjects. For {open_quotes}aA{close_quote} subjects the estimated penetrance value was close to 1 by age 60. For {open_quotes}AA{close_quotes} 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. 10 refs., 1 tab.

Authors:
; ; ;  [1]
  1. INSERM, Paris (France) [and others
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
437191
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Medical Genetics; Journal Volume: 67; Journal Issue: 1; Other Information: PBD: 16 Feb 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; NERVOUS SYSTEM DISEASES; GENETICS; AGE DEPENDENCE; SEX DEPENDENCE; MATHEMATICAL MODELS; PATIENTS; HEREDITARY DISEASES; MENTAL DISORDERS; GENOTYPE; GENES; GENETIC MAPPING; HUMAN CHROMOSOME 21; HUMAN CHROMOSOME 14; DOMINANT MUTATIONS

Citation Formats

Martinez, M., Campion, D., Babron, M.C., and Darpoux, F.C. Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases. United States: N. p., 1996. Web. doi:10.1002/ajmg.1320670102.
Martinez, M., Campion, D., Babron, M.C., & Darpoux, F.C. Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases. United States. doi:10.1002/ajmg.1320670102.
Martinez, M., Campion, D., Babron, M.C., and Darpoux, F.C. 1996. "Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases". United States. doi:10.1002/ajmg.1320670102.
@article{osti_437191,
title = {Segregation analysis of Alzheimer pedigrees: Rare Mendelian dominant mutation(s) explain a minority of early-onset cases},
author = {Martinez, M. and Campion, D. and Babron, M.C. and Darpoux, F.C.},
abstractNote = {Segregation analysis of Alzheimer disease (AD) in 92 families ascertained through early-onset ({le}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 {open_quotes}a{close_quotes} 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 {open_quotes}AA{close_quote} but not for {open_quotes}aA{close_quote} subjects. For {open_quotes}aA{close_quote} subjects the estimated penetrance value was close to 1 by age 60. For {open_quotes}AA{close_quotes} 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. 10 refs., 1 tab.},
doi = {10.1002/ajmg.1320670102},
journal = {American Journal of Medical Genetics},
number = 1,
volume = 67,
place = {United States},
year = 1996,
month = 2
}
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