Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation

Neurobiol Aging. 2016 Oct;46:236.e1-6. doi: 10.1016/j.neurobiolaging.2016.06.018. Epub 2016 Jul 4.


We have previously reported the whole genome genotyping analysis of 2 consanguineous siblings clinically diagnosed with early onset Alzheimer's disease (AD). In this analysis, we identified several large regions of homozygosity shared between both affected siblings, which we suggested could be candidate loci for a recessive genetic lesion underlying the early onset AD in these cases. We have now performed exome sequencing in one of these siblings and identified the potential cause of disease: the CTSF c.1243G>A:p.Gly415Arg mutation in homozygosity. Biallelic mutations in this gene have been shown to cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis with some cases resembling the impairment seen in AD.

Keywords: CTSF; Early onset Alzheimer's disease; Exome sequencing; Homozygosity; Kufs disease; Recessive.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics*
  • Cathepsin F / genetics*
  • Consanguinity*
  • Exome / genetics*
  • Genome-Wide Association Study*
  • Homozygote*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neuronal Ceroid-Lipofuscinoses / genetics
  • Sequence Analysis
  • Siblings


  • CTSF protein, human
  • Cathepsin F