Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype

Nicola J. Rutherford, Michael G. Heckman, Mariely DeJesus-Hernandez, Matt C. Baker, Alexandra I. Soto-Ortolaza, Sruti Rayaprolu, Heather Stewart, Elizabeth Finger, Kathryn Volkening, William W. Seeley, Kimmo J. Hatanpaa, Catherine Lomen-Hoerth, Andrew Kertesz, Eileen H. Bigio, Carol Lippa, David S Knopman, Hans A. Kretzschmar, Manuela Neumann, Richard John Caselli, Charles L. WhiteIan R. Mackenzie, Ronald Carl Petersen, Michael J. Strong, Bruce L. Miller, Bradley F Boeve, Ryan J. Uitti, Kevin B. Boylan, Zbigniew K Wszolek, Neill R Graff Radford, Dennis W Dickson, Owen A Ross, Rosa V Rademakers

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Expansions of the noncoding GGGGCC hexanucleotide repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study we aimed to determine whether the length of the normal-unexpanded-allele of the GGGGCC repeat in C9ORF72 plays a role in the presentation of disease or affects age at onset in C9ORF72 mutation carriers. We also studied whether the GGGGCC repeat length confers risk or affects age at onset in FTD and ALS patients without C9ORF72 repeat expansions. C9ORF72 genotyping was performed in 580 FTD, 995 ALS, and 160 FTD-ALS patients, and 1444 controls, leading to the identification of 211 patients with pathogenic C9ORF72 repeat expansions. No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume33
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Chromosomes, Human, Pair 9
Open Reading Frames
Alleles
Phenotype
Age of Onset
Mutation
Frontotemporal Dementia With Motor Neuron Disease

Keywords

  • Amyotrophic lateral sclerosis
  • Association study
  • C9ORF72
  • Frontotemporal dementia
  • Repeat-expansion disease

ASJC Scopus subject areas

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

Cite this

Rutherford, N. J., Heckman, M. G., DeJesus-Hernandez, M., Baker, M. C., Soto-Ortolaza, A. I., Rayaprolu, S., ... Rademakers, R. V. (2012). Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype. Neurobiology of Aging, 33(12). https://doi.org/10.1016/j.neurobiolaging.2012.07.005

Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype. / Rutherford, Nicola J.; Heckman, Michael G.; DeJesus-Hernandez, Mariely; Baker, Matt C.; Soto-Ortolaza, Alexandra I.; Rayaprolu, Sruti; Stewart, Heather; Finger, Elizabeth; Volkening, Kathryn; Seeley, William W.; Hatanpaa, Kimmo J.; Lomen-Hoerth, Catherine; Kertesz, Andrew; Bigio, Eileen H.; Lippa, Carol; Knopman, David S; Kretzschmar, Hans A.; Neumann, Manuela; Caselli, Richard John; White, Charles L.; Mackenzie, Ian R.; Petersen, Ronald Carl; Strong, Michael J.; Miller, Bruce L.; Boeve, Bradley F; Uitti, Ryan J.; Boylan, Kevin B.; Wszolek, Zbigniew K; Graff Radford, Neill R; Dickson, Dennis W; Ross, Owen A; Rademakers, Rosa V.

In: Neurobiology of Aging, Vol. 33, No. 12, 12.2012.

Research output: Contribution to journalArticle

Rutherford, NJ, Heckman, MG, DeJesus-Hernandez, M, Baker, MC, Soto-Ortolaza, AI, Rayaprolu, S, Stewart, H, Finger, E, Volkening, K, Seeley, WW, Hatanpaa, KJ, Lomen-Hoerth, C, Kertesz, A, Bigio, EH, Lippa, C, Knopman, DS, Kretzschmar, HA, Neumann, M, Caselli, RJ, White, CL, Mackenzie, IR, Petersen, RC, Strong, MJ, Miller, BL, Boeve, BF, Uitti, RJ, Boylan, KB, Wszolek, ZK, Graff Radford, NR, Dickson, DW, Ross, OA & Rademakers, RV 2012, 'Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype', Neurobiology of Aging, vol. 33, no. 12. https://doi.org/10.1016/j.neurobiolaging.2012.07.005
Rutherford NJ, Heckman MG, DeJesus-Hernandez M, Baker MC, Soto-Ortolaza AI, Rayaprolu S et al. Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype. Neurobiology of Aging. 2012 Dec;33(12). https://doi.org/10.1016/j.neurobiolaging.2012.07.005
Rutherford, Nicola J. ; Heckman, Michael G. ; DeJesus-Hernandez, Mariely ; Baker, Matt C. ; Soto-Ortolaza, Alexandra I. ; Rayaprolu, Sruti ; Stewart, Heather ; Finger, Elizabeth ; Volkening, Kathryn ; Seeley, William W. ; Hatanpaa, Kimmo J. ; Lomen-Hoerth, Catherine ; Kertesz, Andrew ; Bigio, Eileen H. ; Lippa, Carol ; Knopman, David S ; Kretzschmar, Hans A. ; Neumann, Manuela ; Caselli, Richard John ; White, Charles L. ; Mackenzie, Ian R. ; Petersen, Ronald Carl ; Strong, Michael J. ; Miller, Bruce L. ; Boeve, Bradley F ; Uitti, Ryan J. ; Boylan, Kevin B. ; Wszolek, Zbigniew K ; Graff Radford, Neill R ; Dickson, Dennis W ; Ross, Owen A ; Rademakers, Rosa V. / Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 12.
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abstract = "Expansions of the noncoding GGGGCC hexanucleotide repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study we aimed to determine whether the length of the normal-unexpanded-allele of the GGGGCC repeat in C9ORF72 plays a role in the presentation of disease or affects age at onset in C9ORF72 mutation carriers. We also studied whether the GGGGCC repeat length confers risk or affects age at onset in FTD and ALS patients without C9ORF72 repeat expansions. C9ORF72 genotyping was performed in 580 FTD, 995 ALS, and 160 FTD-ALS patients, and 1444 controls, leading to the identification of 211 patients with pathogenic C9ORF72 repeat expansions. No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers.",
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T1 - Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype

AU - Rutherford, Nicola J.

AU - Heckman, Michael G.

AU - DeJesus-Hernandez, Mariely

AU - Baker, Matt C.

AU - Soto-Ortolaza, Alexandra I.

AU - Rayaprolu, Sruti

AU - Stewart, Heather

AU - Finger, Elizabeth

AU - Volkening, Kathryn

AU - Seeley, William W.

AU - Hatanpaa, Kimmo J.

AU - Lomen-Hoerth, Catherine

AU - Kertesz, Andrew

AU - Bigio, Eileen H.

AU - Lippa, Carol

AU - Knopman, David S

AU - Kretzschmar, Hans A.

AU - Neumann, Manuela

AU - Caselli, Richard John

AU - White, Charles L.

AU - Mackenzie, Ian R.

AU - Petersen, Ronald Carl

AU - Strong, Michael J.

AU - Miller, Bruce L.

AU - Boeve, Bradley F

AU - Uitti, Ryan J.

AU - Boylan, Kevin B.

AU - Wszolek, Zbigniew K

AU - Graff Radford, Neill R

AU - Dickson, Dennis W

AU - Ross, Owen A

AU - Rademakers, Rosa V

PY - 2012/12

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N2 - Expansions of the noncoding GGGGCC hexanucleotide repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study we aimed to determine whether the length of the normal-unexpanded-allele of the GGGGCC repeat in C9ORF72 plays a role in the presentation of disease or affects age at onset in C9ORF72 mutation carriers. We also studied whether the GGGGCC repeat length confers risk or affects age at onset in FTD and ALS patients without C9ORF72 repeat expansions. C9ORF72 genotyping was performed in 580 FTD, 995 ALS, and 160 FTD-ALS patients, and 1444 controls, leading to the identification of 211 patients with pathogenic C9ORF72 repeat expansions. No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers.

AB - Expansions of the noncoding GGGGCC hexanucleotide repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this study we aimed to determine whether the length of the normal-unexpanded-allele of the GGGGCC repeat in C9ORF72 plays a role in the presentation of disease or affects age at onset in C9ORF72 mutation carriers. We also studied whether the GGGGCC repeat length confers risk or affects age at onset in FTD and ALS patients without C9ORF72 repeat expansions. C9ORF72 genotyping was performed in 580 FTD, 995 ALS, and 160 FTD-ALS patients, and 1444 controls, leading to the identification of 211 patients with pathogenic C9ORF72 repeat expansions. No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers.

KW - Amyotrophic lateral sclerosis

KW - Association study

KW - C9ORF72

KW - Frontotemporal dementia

KW - Repeat-expansion disease

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