Diversity of Cognitive Phenotypes Associated with C9ORF72 Hexanucleotide Expansion

J Alzheimers Dis. 2016 Feb 26;52(1):25-31. doi: 10.3233/JAD-150922.

Abstract

For diagnostic purposes, we screened for the C9ORF72 mutation in a) 162 FTLD cases, and b) 145 cases with other diagnoses but with some frontotemporal features or manifestations previously reported in C9 carriers. Ten cases (onset 50 to 75 years) harbored the expansion: seven had FTLD syndromes (4.3% of total, 11% of familial cases), and three (2%) had a different diagnosis. All positive cases had family history of dementia, psychiatric disease, or ALS, but only 20% of families with mixed FTLD/ALS phenotypes carried the expansion. Language impairment was the most common symptom, followed by behavioral changes, memory deficits, and parkinsonism. C9ORF72 mutation has a low frequency in our dementia series and very diverse clinical manifestations.

Keywords: C9ORF72 gene; frontotemporal dementia; hexanucleotide expansion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Apolipoprotein E4 / genetics
  • C9orf72 Protein
  • Cognition*
  • DNA Repeat Expansion*
  • Family
  • Female
  • Follow-Up Studies
  • Frontotemporal Lobar Degeneration / epidemiology
  • Frontotemporal Lobar Degeneration / genetics*
  • Frontotemporal Lobar Degeneration / psychology*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotyping Techniques
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Proteins / genetics*
  • Spain / epidemiology

Substances

  • Apolipoprotein E4
  • C9orf72 Protein
  • C9orf72 protein, human
  • Proteins