Screening for C9ORF72 repeat expansion in FTLD

Neurobiol Aging. 2012 Aug;33(8):1850.e1-11. doi: 10.1016/j.neurobiolaging.2012.02.017. Epub 2012 Mar 27.


In the present study we aimed to determine the prevalence of C9ORF72 GGGGCC hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration (FTLD) patients and 174 neurologically normal controls. We identified the hexanucleotide repeat, in the pathogenic range, in 4 (2 bv-frontotemporal dementia (FTD) and 2 FTD-amyotrophic lateral sclerosis [ALS]) out of 53 patients and 1 neurologically normal control. Interestingly, 2 of the C9ORF72 expansion carriers also carried 2 novel missense mutations in GRN (Y294C) and in PSEN-2(I146V). Further, 1 of the C9ORF72 expansion carriers, for whom pathology was available, showed amyloid plaques and tangles in addition to TAR (trans-activation response) DNA-binding protein (TDP)-43 pathology. In summary, our findings suggest that the hexanucleotide expansion is probably associated with ALS, FTD, or FTD-ALS and occasional comorbid conditions such as Alzheimer's disease. These findings are novel and need to be cautiously interpreted and most importantly replicated in larger numbers of samples.

Publication types

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

MeSH terms

  • Aged
  • C9orf72 Protein
  • Female
  • Frontotemporal Lobar Degeneration / epidemiology*
  • Frontotemporal Lobar Degeneration / genetics*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence
  • Proteins / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Risk Factors
  • United States / epidemiology


  • C9orf72 Protein
  • C9orf72 protein, human
  • Genetic Markers
  • Proteins