Segregation analysis of Alzheimer pedigrees: rare Mendelian dominant mutation(s) explain a minority of early-onset cases. French Alzheimer Collaborative Group

Am J Med Genet. 1996 Feb 16;67(1):9-12. doi: 10.1002/ajmg.1320670102.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Age of Onset
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics*
  • Female
  • Genes, Dominant*
  • Humans
  • Male
  • Mathematical Computing
  • Mutation*
  • Pedigree
  • Risk Factors
  • Sex Factors