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

doi:10.1016/j.neurobiolaging.2012.02.017

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^*

^*Corresponding author for this work

Physical Medicine and Rehabilitation

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

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 language	English (US)
Pages (from-to)	1850.e1-1850.e11
Journal	Neurobiology of Aging
Volume	33
Issue number	8
DOIs	https://doi.org/10.1016/j.neurobiolaging.2012.02.017
State	Published - Aug 2012

Keywords

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

ASJC Scopus subject areas

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

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Ferrari, R., Mok, K., Moreno, J. H., Cosentino, S., Goldman, J., Pietrini, P., Mayeux, R., Tierney, M. C., Kapogiannis, D., Jicha, G. A., Murrell, J. R., Ghetti, B., Wassermann, E. M., Grafman, J., Hardy, J., Huey, E. D., & Momeni, P. (2012). Screening for C9ORF72 repeat expansion in FTLD. Neurobiology of Aging, 33(8), 1850.e1-1850.e11. 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. pp. 1850.e1-1850.e11.

@article{f26b714a653443e5996bdac7141bab78,

title = "Screening for C9ORF72 repeat expansion in FTLD",

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.",

keywords = "Alzheimer's disease, Bv-FTD, C9ORF72, FTD-ALS, FTLD, GRN, PSEN-2",

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

note = "Funding Information: PM molecular genetics work is funded by the office of the Dean of the School of Medicine, department of Internal Medicine, at Texas Tech Health Sciences Center. J.H.'s work on FTD GWAS is supported partly by a grant from Alzheimer's Research UK. This research was supported in part by the Intramural Research Programs of the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. E.D.H.'s work is supported by NIH/NINDS grant 5R00NS060766 . J.G.'s work is supported by the NINDS Intramural Research Program. D.G.'s work was supported by NIH grant PHS P30 AG 10133 . The authors thank Mike Hubank and Kerra Pearce at the Genomic core facility at the Institute of Child Health (ICH), University College London (UCL) for assisting R.F. in performing Illumina genotyping experiments, and Cynthia Crews, Anne Leopold, and Karen DeTucci for the study coordination. ",

year = "2012",

month = aug,

doi = "10.1016/j.neurobiolaging.2012.02.017",

language = "English (US)",

volume = "33",

pages = "1850.e1--1850.e11",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

number = "8",

}

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, pp. 1850.e1-1850.e11. 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, p. 1850.e1-1850.e11.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Screening for C9ORF72 repeat expansion in FTLD

AU - Ferrari, Raffaele

AU - Mok, Kin

AU - Moreno, Jorge H.

AU - Cosentino, Stephanie

AU - Goldman, Jill

AU - Pietrini, Pietro

AU - Mayeux, Richard

AU - Tierney, Michael C.

AU - Kapogiannis, Dimitrios

AU - Jicha, Gregory A.

AU - Murrell, Jill R.

AU - Ghetti, Bernardino

AU - Wassermann, Eric M.

AU - Grafman, Jordan

AU - Hardy, John

AU - Huey, Edward D.

AU - Momeni, Parastoo

N1 - Funding Information: PM molecular genetics work is funded by the office of the Dean of the School of Medicine, department of Internal Medicine, at Texas Tech Health Sciences Center. J.H.'s work on FTD GWAS is supported partly by a grant from Alzheimer's Research UK. This research was supported in part by the Intramural Research Programs of the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. E.D.H.'s work is supported by NIH/NINDS grant 5R00NS060766 . J.G.'s work is supported by the NINDS Intramural Research Program. D.G.'s work was supported by NIH grant PHS P30 AG 10133 . The authors thank Mike Hubank and Kerra Pearce at the Genomic core facility at the Institute of Child Health (ICH), University College London (UCL) for assisting R.F. in performing Illumina genotyping experiments, and Cynthia Crews, Anne Leopold, and Karen DeTucci for the study coordination.

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Bv-FTD

KW - C9ORF72

KW - FTD-ALS

KW - FTLD

KW - GRN

KW - PSEN-2

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U2 - 10.1016/j.neurobiolaging.2012.02.017

DO - 10.1016/j.neurobiolaging.2012.02.017

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C2 - 22459598

AN - SCOPUS:84861861630

VL - 33

SP - 1850.e1-1850.e11

JO - Neurobiology of Aging

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