Nonsense mutation in PRNP associated with clinical Alzheimer's disease

Neurobiol Aging. 2014 Nov;35(11):2656.e13-2656.e16. doi: 10.1016/j.neurobiolaging.2014.05.013. Epub 2014 May 27.


Here, we describe a nonsense haplotype in PRNP associated with clinical Alzheimer's disease. The patient presented an early-onset of cognitive decline with memory loss as the primary cognitive problem. Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes.

Keywords: Alzheimer's disease; Exome sequencing; Nonsense mutation; PRNP; Prion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alzheimer Disease / genetics*
  • Codon, Nonsense / genetics*
  • Cognition Disorders / genetics
  • Exome / genetics
  • Genetic Association Studies*
  • Genotype
  • Haplotypes / genetics
  • Homozygote
  • Humans
  • Memory Disorders / genetics
  • Phenotype
  • Prion Proteins
  • Prions / genetics*
  • Sequence Analysis


  • Codon, Nonsense
  • PRNP protein, human
  • Prion Proteins
  • Prions