Mutation burden profile in familial Alzheimer's disease cases from India

Neurobiol Aging. 2018 Apr;64:158.e7-158.e13. doi: 10.1016/j.neurobiolaging.2017.12.002. Epub 2017 Dec 12.

Abstract

This study attempts to identify coding risk variants in genes previously implicated in Alzheimer's disease (AD) pathways, through whole-exome sequencing of subjects (N = 17) with AD, with a positive family history of dementia (familial AD). We attempted to evaluate the mutation burden in genes encoding amyloid precursor protein metabolism and previously linked to risk of dementias. Novel variants were identified in genes involved in amyloid precursor protein metabolism such as PSEN1 (chr 14:73653575, W161C, tgg > tgT), PLAT (chr 8:42039530,G272R), and SORL1 (chr11:121414373,G601D). The mutation burden assessment of dementia-related genes for all 17 cases revealed 45 variants, which were either shared across subjects, or were present in just the 1 patient. The study shows that the clinical characteristics, and genetic correlates, obtained in this sample are broadly comparable to the other studies that have investigated familial forms of AD. Our study identifies rare deleterious genetic variations, in the coding region of genes involved in amyloid signaling, and other dementia-associated pathways.

Keywords: Alzheimer's disease; Clinical symptoms; Coding variation; Mutation burden; Whole-exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / metabolism*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Humans
  • India
  • LDL-Receptor Related Proteins / genetics
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Mutation*
  • Presenilin-1 / genetics
  • Risk
  • Signal Transduction / genetics
  • Tissue Plasminogen Activator / genetics
  • Whole Exome Sequencing

Substances

  • Amyloid beta-Protein Precursor
  • LDL-Receptor Related Proteins
  • Membrane Transport Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • SORL1 protein, human
  • PLAT protein, human
  • Tissue Plasminogen Activator