Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome

Mariely DeJesus-Hernandez; Sruti Rayaprolu; Alexandra I. Soto-Ortolaza; Nicola J. Rutherford; Michael G. Heckman; Sharleen Traynor; Audrey Strongosky; Neill Graff-Radford; Jay Van Gerpen; Ryan J. Uitti; Jerry J. Shih; Siong Chi Lin; Zbigniew K. Wszolek; Rosa Rademakers; Owen A. Ross

doi:10.1016/j.parkreldis.2012.09.013

Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome

Mariely DeJesus-Hernandez, Sruti Rayaprolu, Alexandra I. Soto-Ortolaza, Nicola J. Rutherford, Michael G. Heckman, Sharleen Traynor, Audrey Strongosky, Neill Graff-Radford, Jay Van Gerpen, Ryan J. Uitti, Jerry J. Shih, Siong Chi Lin, Zbigniew K. Wszolek, Rosa Rademakers, Owen A. Ross

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

28 Scopus citations

Abstract

The hexanucleotide expanded repeat (GGGGCC) in intron 1 of the C9orf72 gene is recognized as the most common genetic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, as part of the clinical phenotype, some patients present with parkinsonism. The present study investigated the potential expansion or association of the C9orf72 repeat length with susceptibility to Parkinson's disease and related disorders, essential tremor and restless legs syndrome. One restless legs syndrome patient was shown to harbor a repeat expansion, however on clinical follow-up this patient was observed to have developed frontotemporal dementia. There was no evidence of association of repeat length on disease risk or age-at-onset for any of the three disorders. Therefore the C9orf72 hexanucleotide repeat expansion appears to be specific to TDP-43 driven amyotrophic lateral sclerosis and dementia.

Original language	English (US)
Pages (from-to)	198-201
Number of pages	4
Journal	Parkinsonism and Related Disorders
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/j.parkreldis.2012.09.013
State	Published - Feb 2013

Keywords

C9orf72
ET
Expanded repeat
Genetic association
PD
RLS

ASJC Scopus subject areas

Neurology
Geriatrics and Gerontology
Clinical Neurology

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10.1016/j.parkreldis.2012.09.013

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DeJesus-Hernandez, M., Rayaprolu, S., Soto-Ortolaza, A. I., Rutherford, N. J., Heckman, M. G., Traynor, S., Strongosky, A., Graff-Radford, N., Van Gerpen, J., Uitti, R. J., Shih, J. J., Lin, S. C., Wszolek, Z. K., Rademakers, R., & Ross, O. A. (2013). Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome. Parkinsonism and Related Disorders, 19(2), 198-201. https://doi.org/10.1016/j.parkreldis.2012.09.013

DeJesus-Hernandez, M, Rayaprolu, S, Soto-Ortolaza, AI, Rutherford, NJ, Heckman, MG, Traynor, S, Strongosky, A, Graff-Radford, N, Van Gerpen, J, Uitti, RJ, Shih, JJ, Lin, SC, Wszolek, ZK, Rademakers, R & Ross, OA 2013, 'Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome', Parkinsonism and Related Disorders, vol. 19, no. 2, pp. 198-201. https://doi.org/10.1016/j.parkreldis.2012.09.013

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title = "Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome",

abstract = "The hexanucleotide expanded repeat (GGGGCC) in intron 1 of the C9orf72 gene is recognized as the most common genetic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, as part of the clinical phenotype, some patients present with parkinsonism. The present study investigated the potential expansion or association of the C9orf72 repeat length with susceptibility to Parkinson's disease and related disorders, essential tremor and restless legs syndrome. One restless legs syndrome patient was shown to harbor a repeat expansion, however on clinical follow-up this patient was observed to have developed frontotemporal dementia. There was no evidence of association of repeat length on disease risk or age-at-onset for any of the three disorders. Therefore the C9orf72 hexanucleotide repeat expansion appears to be specific to TDP-43 driven amyotrophic lateral sclerosis and dementia.",

keywords = "C9orf72, ET, Expanded repeat, Genetic association, PD, RLS",

author = "Mariely DeJesus-Hernandez and Sruti Rayaprolu and Soto-Ortolaza, {Alexandra I.} and Rutherford, {Nicola J.} and Heckman, {Michael G.} and Sharleen Traynor and Audrey Strongosky and Neill Graff-Radford and {Van Gerpen}, Jay and Uitti, {Ryan J.} and Shih, {Jerry J.} and Lin, {Siong Chi} and Wszolek, {Zbigniew K.} and Rosa Rademakers and Ross, {Owen A.}",

note = "Funding Information: We would like to thank all those who have contributed to our research, particularly the patients and families who donated DNA samples for this work. This work is supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50NS072187 ), NINDS R01NS078086 and the Mayo Clinic Clinical Research Program (MCF # 90052030 ). RR is supported by NIH grants R01AG026251 and the ALS Therapy Alliance . ",

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AU - DeJesus-Hernandez, Mariely

AU - Rayaprolu, Sruti

AU - Soto-Ortolaza, Alexandra I.

AU - Rutherford, Nicola J.

AU - Heckman, Michael G.

AU - Traynor, Sharleen

AU - Strongosky, Audrey

AU - Graff-Radford, Neill

AU - Van Gerpen, Jay

AU - Uitti, Ryan J.

AU - Shih, Jerry J.

AU - Lin, Siong Chi

AU - Wszolek, Zbigniew K.

AU - Rademakers, Rosa

AU - Ross, Owen A.

N1 - Funding Information: We would like to thank all those who have contributed to our research, particularly the patients and families who donated DNA samples for this work. This work is supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50NS072187 ), NINDS R01NS078086 and the Mayo Clinic Clinical Research Program (MCF # 90052030 ). RR is supported by NIH grants R01AG026251 and the ALS Therapy Alliance .

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N2 - The hexanucleotide expanded repeat (GGGGCC) in intron 1 of the C9orf72 gene is recognized as the most common genetic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, as part of the clinical phenotype, some patients present with parkinsonism. The present study investigated the potential expansion or association of the C9orf72 repeat length with susceptibility to Parkinson's disease and related disorders, essential tremor and restless legs syndrome. One restless legs syndrome patient was shown to harbor a repeat expansion, however on clinical follow-up this patient was observed to have developed frontotemporal dementia. There was no evidence of association of repeat length on disease risk or age-at-onset for any of the three disorders. Therefore the C9orf72 hexanucleotide repeat expansion appears to be specific to TDP-43 driven amyotrophic lateral sclerosis and dementia.

AB - The hexanucleotide expanded repeat (GGGGCC) in intron 1 of the C9orf72 gene is recognized as the most common genetic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, as part of the clinical phenotype, some patients present with parkinsonism. The present study investigated the potential expansion or association of the C9orf72 repeat length with susceptibility to Parkinson's disease and related disorders, essential tremor and restless legs syndrome. One restless legs syndrome patient was shown to harbor a repeat expansion, however on clinical follow-up this patient was observed to have developed frontotemporal dementia. There was no evidence of association of repeat length on disease risk or age-at-onset for any of the three disorders. Therefore the C9orf72 hexanucleotide repeat expansion appears to be specific to TDP-43 driven amyotrophic lateral sclerosis and dementia.

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Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome

Abstract

Keywords

ASJC Scopus subject areas

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