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

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:
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
Sponsoring Org:
USDOE
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