Unusual Segregation of APP Mutations in Monogenic Alzheimer Disease

Neurodegener Dis. 2019;19(2):96-100. doi: 10.1159/000502906. Epub 2019 Oct 2.

Abstract

APP gene mutations causing Alzheimer disease (AD) segregate in an autosomal dominant pattern. We report on a 40-year-old woman with a severe cognitive decline starting at 36 years, while her affected relatives presented symptoms onset in the 6th decade. The proband carried an APP missense variant in homozygous state (NM_000484.4: c.2032G>A; NP_000475.1: p.Asp678Asn; rs63750064) and showed a more severe clinical picture than the other AD relatives, as regards the age of onset and the rate of disease progression. This mutation behaves as a semi-dominant trait. The very rare chance of studying APP mutations in the homozygous state demonstrates they are not always dominant and other segregation models are possible.

Keywords: APP; Alzheimer; Dementia; Neurogenetics; Semi-dominant pattern.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics*
  • Disease Progression
  • Female
  • Humans
  • Mutation*
  • Phenotype

Substances

  • Amyloid beta-Protein Precursor