Screening for C9ORF72 repeat expansion in FTLD

Raffaele Ferrari, Kin Mok, Jorge H. Moreno, Stephanie Cosentino, Jill Goldman, Pietro Pietrini, Richard Mayeux, Michael C. Tierney, Dimitrios Kapogiannis, Gregory A. Jicha, Jill R. Murrell, Bernardino Ghetti, Eric M. Wassermann, Jordan Grafman, John Hardy, Edward D. Huey, Parastoo Momeni

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalNeurobiology of Aging
Volume33
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Frontotemporal Lobar Degeneration
Pathology
Frontotemporal Dementia
Amyloid Plaques
Amyotrophic Lateral Sclerosis
DNA-Binding Proteins
Missense Mutation
Alzheimer Disease
Frontotemporal Dementia With Motor Neuron Disease

Keywords

  • Alzheimer's disease
  • Bv-FTD
  • C9ORF72
  • FTD-ALS
  • FTLD
  • GRN
  • PSEN-2

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Ferrari, R., Mok, K., Moreno, J. H., Cosentino, S., Goldman, J., Pietrini, P., ... Momeni, P. (2012). Screening for C9ORF72 repeat expansion in FTLD. Neurobiology of Aging, 33(8). https://doi.org/10.1016/j.neurobiolaging.2012.02.017

Screening for C9ORF72 repeat expansion in FTLD. / Ferrari, Raffaele; Mok, Kin; Moreno, Jorge H.; Cosentino, Stephanie; Goldman, Jill; Pietrini, Pietro; Mayeux, Richard; Tierney, Michael C.; Kapogiannis, Dimitrios; Jicha, Gregory A.; Murrell, Jill R.; Ghetti, Bernardino; Wassermann, Eric M.; Grafman, Jordan; Hardy, John; Huey, Edward D.; Momeni, Parastoo.

In: Neurobiology of Aging, Vol. 33, No. 8, 08.2012.

Research output: Contribution to journalArticle

Ferrari, R, Mok, K, Moreno, JH, Cosentino, S, Goldman, J, Pietrini, P, Mayeux, R, Tierney, MC, Kapogiannis, D, Jicha, GA, Murrell, JR, Ghetti, B, Wassermann, EM, Grafman, J, Hardy, J, Huey, ED & Momeni, P 2012, 'Screening for C9ORF72 repeat expansion in FTLD', Neurobiology of Aging, vol. 33, no. 8. https://doi.org/10.1016/j.neurobiolaging.2012.02.017
Ferrari R, Mok K, Moreno JH, Cosentino S, Goldman J, Pietrini P et al. Screening for C9ORF72 repeat expansion in FTLD. Neurobiology of Aging. 2012 Aug;33(8). https://doi.org/10.1016/j.neurobiolaging.2012.02.017
Ferrari, Raffaele ; Mok, Kin ; Moreno, Jorge H. ; Cosentino, Stephanie ; Goldman, Jill ; Pietrini, Pietro ; Mayeux, Richard ; Tierney, Michael C. ; Kapogiannis, Dimitrios ; Jicha, Gregory A. ; Murrell, Jill R. ; Ghetti, Bernardino ; Wassermann, Eric M. ; Grafman, Jordan ; Hardy, John ; Huey, Edward D. ; Momeni, Parastoo. / Screening for C9ORF72 repeat expansion in FTLD. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 8.
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abstract = "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.",
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