C9ORF72 expansion in amyotrophic lateral sclerosis/frontotemporal dementia also causes parkinsonism
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C9orf72 expansion mutations are associated with ALS/FTLD and also with symptoms reminiscent of Parkinson disease, Alzheimer disease, Huntington disease, and corticobasal syndrome.
“For instance, C9orf72 expansion mutations are associated not only with ALS/FTLD, but also with symptoms reminiscent of Parkinson disease, Alzheimer disease, Huntington disease, and corticobasal syndrome, reinforcing the imperfect connection between clinical and molecular phenotypes and emphasizing the need for molecular diagnostics [155–164].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [163]
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DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · see citing works
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409 · see citing works
Self-citationAl-Sarraj, S., King, A., Troakes, C., Smith, B., Maekawa, S., Bodi, I., Rogelj, B., Al-Chalabi, A., Hortobágyi, T., & Shaw, C. E. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0911-2 · Cited by 475 · see citing works
PARKINSONISM-DEMENTIA COMPLEX, AN ENDEMIC DISEASE ON THE ISLAND OF GUAM
Hirano, A., Kurland, L. T., Krooth, R. S., & Lessell, S. (1961) · Brain · doi:10.1093/brain/84.4.642 · Cited by 419 · see citing works
Hudson, A. J. (1981) · Brain · doi:10.1093/brain/104.2.217 · Cited by 369 · see citing works
Murray, M. E., DeJesus‐Hernandez, M., Rutherford, N. J., Baker, M. C., Duara, R., Graff‐Radford, N. R., Wszołek, Z. K., Ferman, T. J., Josephs, K. A., Boylan, K., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0907-y · Cited by 295 · see citing works
Lynch, T., Sano, M. C., Marder, K. S., Bell, K. L., Foster, N. L., Defending, R. F., Sima, A. A. F., Keohane, C., Nygaard, T. G., Fahn, S., et al. (1994) · Neurology · doi:10.1212/wnl.44.10.1878 · Cited by 287 · see citing works
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C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis
Rohrer, J. D., Isaacs, A. M., Mizielinska, S., Mead, S., Lashley, T., Wray, S., Sidle, K. C. L., Fratta, P., Orrell, R. W., Hardy, J., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70233-9 · Cited by 234 · see citing works
The expanding universe of disorders of the basal ganglia
Obeso, J. A., Rodríguez‐Oroz, M., Stamelou, M., Bhatia, K. P., & Burn, D. J. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62418-6 · Cited by 232 · see citing works
Neurotransmitter deficits from frontotemporal lobar degeneration
Murley, A. G., & Rowe, J. B. (2017) · Brain · doi:10.1093/brain/awx327 · Cited by 199 · see citing works
“…in the C9orf72 gene on chromosome 9 is most typically associated with FTD with amyotrophic lateral sclerosis (Rohrer et al. , 2015 a ), but up to half of patients have parkinsonism, with decreased dopamine transporter levels in the basal ganglia (Boeve et al. , 2012; O’Dowd et al. , 2012).”
<i>C9orf72</i> expansions are the most common genetic cause of Huntington disease phenocopies
Hensman Moss, D. J., Poulter, M., Beck, J., Hehir, J., Polke, J. M., Campbell, T., Adamson, G., Mudanohwo, E., McColgan, P., Haworth, A., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000061 · Cited by 203 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
Familial Amyotrophic Lateral Sclerosis
Boylan, K. (2015) · Neurologic Clinics · doi:10.1016/j.ncl.2015.07.001 · Cited by 187 · see citing works
Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum
Cruts, M., Gijselinck, I., Langenhove, T. V., van der Zee, J., & Broeckhoven, C. V. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.010 · Cited by 162 · see citing works
Cooper‐Knock, J., Shaw, P. J., & Kirby, J. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1251-9 · Cited by 163 · see citing works
“It is clear that parkinsonism is over-represented compared to chance in C9ORF72-related ALS cases and their families [3, 4, 35, 36].”
BackgroundGenetics of Frontotemporal Dementia
Olszewska, D. A., Lonergan, R. M., Fallon, E., & Lynch, T. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0707-9 · Cited by 156 · see citing works
Self-citationThe clinical spectrum of sporadic and familial forms of frontotemporal dementia
Woollacott, I., & Rohrer, J. D. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13654 · Cited by 151 · see citing works
“The expansion has also been detected in a few patients who have been clinically diagnosed with another neurodegenerative disorder including idiopathic Parkinson’s disease, (O’Dowd et al. 2012; Cooper-Knock et al. 2013; Lesage et al. 2013), Lewy body dementia (Robinson et al.”
BackgroundStamelou, M., Quinn, N. P., & Bhatia, K. P. (2013) · Movement Disorders · doi:10.1002/mds.25509 · Cited by 124 · see citing works
Parkinsonism, movement disorders and genetics in frontotemporal dementia
Baizabal-Carvallo, J. F., & Jankovic, J. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.14 · Cited by 121 · see citing works
Parkinsonian syndrome in familial frontotemporal dementia
Siuda, J., Fujioka, S., & Wszolek, Z. K. (2014) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2014.06.004 · Cited by 96 · see citing works
“Parkinsonism in C9ORF72 FTD patients may remain pure, without associated cognitive deficits or dementia for over 10 years, but this is rare [46, 47].”
BackgroundChipika, R. H., Finegan, E., Shing, S. L. H., McKenna, M. C., Christidi, F., Chang, K. M., Doherty, M. A., Hengeveld, J. C., Vajda, A., Pender, N. P., et al. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102300 · Cited by 76 · see citing works
Self-citationC9ORF72 expansions, parkinsonism, and Parkinson disease
Cooper‐Knock, J., Frolov, A., Highley, J. R., Charlesworth, G., Kirby, J., Milano, A., Hartley, J. A., Ince, P. G., McDermott, C. J., Lashley, T., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a2cc38 · Cited by 64 · see citing works
Stamelou, M., & Höglinger, G. U. (2013) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283632da6 · Cited by 64 · see citing works
The C9ORF72 expansion mutation: gene structure, phenotypic and diagnostic issues
Woollacott, I., & Mead, S. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1253-7 · Cited by 63 · see citing works
Association Studies of MMP-9 in Parkinson’s Disease and Amyotrophic Lateral Sclerosis
He, X., Zhang, L., Yao, X., Hu, J., Yu, L., Jia, H., An, R., Liu, Z., & Xu, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073777 · Cited by 59 · see citing works
Bourinaris, T., & Houlden, H. (2018) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12677 · Cited by 54 · see citing works
“Patients with C9orf72 that manifest parkinsonian symptoms were reported to have a typical presentation that is commonly asymmetric onset akinetic-rigid syndrome with prominent bradykinesia and little or no tremor.(12,14,42,61) Positive family history was commonly reported and included FTD/ALS, parkinsonism, and other…”
BackgroundParkinson disease is not associated with C9ORF72 repeat expansions
Harms, M. B., Neumann, D. A., Benítez, B. A., Cooper, B., Carrell, D., Racette, B. A., Perlmutter, J. S., Goate, A., & Cruchaga, C. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.10.001 · Cited by 43 · see citing works
“Because some repeat expansion carriers have parkinsonism (Luigetti et al., in press; O’Dowd et al., 2012), we sought to determine if C9ORF72 repeat expansions cause Parkinson’s disease (PD) by screening a large clinic cohort.”
C9orf72 mutation is rare in Alzheimer's disease, Parkinson's disease, and essential tremor in China
Jiao, B., Guo, J., Wang, Y., Yan, X., Zhou, L., Liu, X., Zhang, F.-F., Zhou, Y., Xia, K., Tang, B., et al. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00164 · Cited by 42 · see citing works
“Given the overlapping of clinical phenotypes and pathological characteristics between these two diseases and Alzheimer’s disease (AD), Parkinson’s disease (PD), and essential tremor (ET), we speculated regarding whether C9orf72 repeat expansions also play a major role in these three diseases.”
BackgroundŁukaszewicz‐Zając, M., Mroczko, B., & Słowik, A. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1205-3 · Cited by 41 · see citing works
Wilke, C., Pomper, J. K., Biskup, S., Puskás, C., Berg, D., & Synofzik, M. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8021-7 · Cited by 43 · see citing works
“Regarding hypokinetic movement disorders, C9orf72-positive individuals may present with PD [4, 9, 11, 28, 30, 31, 36, 37], PSP (as demonstrated by our case), multiple system atrophy [7], corticobasal syndrome [8] and overlap syndromes [23, 24].”
BackgroundTakada, L. T., & Sha, S. J. (2012) · Alzheimer s Research & Therapy · doi:10.1186/alzrt141 · Cited by 35 · see citing works
“bvFTD, FTD-MND and ALS are the most commonly observed phenotypes, but nonfl uent variant primary progressive aphasia, Alzheimer’s disease, parkinsonism, corticobasal syndrome, and ataxia have also been reported, albeit infrequently [4,6,8-10].”
BackgroundC9orf72 repeat expansions are restricted to the ALS-FTD spectrum
Ticozzi, N., Tiloca, C., Calini, D., Gagliardi, S., Altieri, A., Colombrita, C., Cereda, C., Ratti, A., Pezzoli, G., Borroni, B., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.037 · Cited by 34 · see citing works
“These recent observations broaden the clinical phenotype spectrum associated with C9orf72, suggesting the existence of a novel C9orf72-positive ALS-parkinsonism nosological entity (O’Dowd et al., 2012).”
BackgroundC9ORF72 Mutations in Neurodegenerative Diseases
Liu, Y., Yu, J., Zong, Y., Zhou, J., & Tan, L. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8528-1 · Cited by 33 · see citing works
Parkinsonism in frontotemporal dementias
Rowe, J. B. (2019) · International review of neurobiology · doi:10.1016/bs.irn.2019.10.012 · Cited by 33 · see citing works
Gasca‐Salas, C., Masellis, M., Khoo, E., Shah, B., Fisman, D. N., Lang, A. E., & Kleiner‐Fisman, G. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153852 · Cited by 30 · see citing works
“…C9orf72 mutations presenting with motor neuron disease (MND) [37, 85] and another 2 subjects also with C9orf72 mutations presenting with MD and MND [82, 85], all subjects with movement symptoms at onset presented with a movement disorder including clinical syndromes of Parkinsonism, CBS or PSPS.”
Guo, X. Y., Chen, Y. P., Song, W., Zhao, B., Cao, B., Wei, Q. Q., Ou, R., Yang, Y., Yuan, L. X., & Shang, H. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.014 · Cited by 29 · see citing works
“In addition, guanine (CAG)n expansions in the ATXN2 gene and hexanucleotide repeat expansions in the C9ORF72 gene are involved in both ALS and PD (Furtado et al., 2004; O’Dowd et al., 2012; Ross et al., 2011).”
BackgroundDombroski, B. A., Galasko, D. R., Mata, I. F., Zabetian, C. P., Craig, U.-K., Garruto, R. M., Oyanagi, K., & Schellenberg, G. D. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.1817 · Cited by 24 · see citing works
“Parkinsonism is also observed in some cases of C9orf72 expansion.(14) A study(15) of Kii Peninsula families with ALS Author Aff Departmen Laboratory School of M of Pennsylv (Drs Domb Schellenber Neuroscien California– (Dr Galask Puget Soun System and Neurology, Washington and Zabetia Biomedical Neuroscien Program in A…”
BackgroundCarecchio, M., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E. A., Comi, C., Terazzi, E., & Cantello, R. M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-131151 · Cited by 19 · see citing works
“Recently, O’Dowd and colleagues described a patient presenting with a complex phenotype including amyotrophic lateral sclerosis, FTD, and parkinsonism also showed abnormal DAT-Scan [27]. dopamine synthesis in FTLD have not been performed .”
Samra, K., MacDougall, A. M., Peakman, G., Bouzigues, A., Bocchetta, M., Cash, D. M., Greaves, C. V., Convery, R. S., Swieten, J. C. V., Jiskoot, L. C., et al. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11442-y · Cited by 18 · see citing works
Waldö, M. L., Gustafson, L., Nilsson, K. H., Traynor, B. J., Renton, A. E., Englund, E. M., & Passant, U. (2013) · Europe PMC (PubMed Central) · Cited by 17 · see citing works
Self-citationXu, X., Su, Y., Zou, Z., Zhou, Y., & Yan, J. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.53550 · Cited by 14 · see citing works
“Only a few studies have reported other symptoms, mainly Parkinsonism and psychotic features, in several C9ORF72-positive FTD/ ALS patients [44-46].”
BackgroundResultGagliardi, D., Costamagna, G., Taiana, M. M., Andreoli, L., Biella, F., Bersani, M., Bresolin, N., Comi, G. P., & Corti, S. P. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101172 · Cited by 11 · see citing works
Genetic mimics of the non-genetic atypical parkinsonian disorders – the ‘atypical’ atypical
Giagkou, N., Bhatia, K. P., Höglinger, G. U., & Stamelou, M. (2019) · International review of neurobiology · doi:10.1016/bs.irn.2019.10.008 · Cited by 11 · see citing works
Molecular Genetics of Frontotemporal Dementia
Ferrari, R., Thumma, A., & Momeni, P. (2013) · Wiley eBooks · doi:10.1002/9780470015902.a0024457 · Cited by 10 · see citing works
C9orf72 hexanucleotide repeat allele tagging SNPs: Associations with ALS risk and longevity
Kaivola, K., Pirinen, M., Laaksovirta, H., Jansson, L., Rautila, O. S., Launes, J., Hokkanen, L., Lahti, J. M. T., Eriksson, J. G., Strandberg, T. E., et al. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1087098 · Cited by 7 · see citing works
“The same mutation has also been reported, although less commonly, in other neurodegenerative conditions, such as Alzheimer’s disease, parkinsonism, Huntingtonlike, corticobasal syndrome, olivopontocerebellar degeneration and idiopathic normal pressure hydrocephalus (Beck et al., 2013; Liu et al., 2014; Korhonen et al.…”
BackgroundZubizarreta, I. K., Manero-Azua, Á., Afonso-Agüera, J., & de Nanclares, G. P. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13091396 · Cited by 7 · see citing works
Mehrabian, S., Thonberg, H., Raycheva, M. R., Lilius, L., Stoyanova, K., Forsell, C., Cavallin, L., Nesheva, D. V., Westman, E., Toncheva, D. I., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0208383 · Cited by 6 · see citing works
Aloisio, S., Satolli, S., Bellini, G., & Lopriore, P. (2023) · Neurological Sciences · doi:10.1007/s10072-023-07044-9 · Cited by 4 · see citing works
Mantero, V., Tarlarini, C., Aliprandi, A., Lauria, G., Rigamonti, A., Abate, L., Origone, P., Mandich, P., Penco, S., & Salmaggi, A. (2017) · Journal of Genetic Counseling · doi:10.1007/s10897-017-0088-5 · Cited by 3 · see citing works
Levodopa responsive asymmetric parkinsonism as clinical presentation of progranulin gene mutation.
Biagioli, N., Cavallieri, F., Marti, A., Rauso, G. D., Fioravanti, V., Monfrini, E., Gasparini, F., Beltrami, D., Grisanti, S., Rossi, J., et al. (2023) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2023.120737 · Cited by 2 · see citing works
Hu, Z., Yan, Q., Wan, J., Fan, Y., & Liu, J. (2025) · Movement Disorders · doi:10.1002/mds.70081 · Cited by 1 · see citing works
“35 The C9ORF72 repeat expansion is the most common genetic cause of ALS and FTD, 4,36 and its association with PD has been reported in various cohorts, albeit with a lower frequency.”
Movement disorders 1 The expanding universe of disorders of the basal ganglia
Obeso, J. A., Rodríguez‐Oroz, M., Stamelou, M., Bhatia, K. P., & Burn, D. J. (2014) · Cited by 1 · see citing works
Commentary: The C9orf72 Repeat Expansion Disrupts Nucleocytoplasmic Transport
Munteanu, T., & Lynch, T. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00051 · Cited by 1 · see citing works
Self-citationWaldö, M. L., Gustafson, L., Nilsson, K. H., Traynor, B. J., Renton, A. E., Elisabet, & Passant, U. (2013)
Self-citationCognitive Sub-groups in ALS: Neuroanatomical Associations and Theory of Mind Impairments
Chenji, S. (2018) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3st7fc7m
de Calbiac, H. (2019) · theses.fr (ABES) · doi:10.70675/bafe951fz8332z4b0azb55bzac8a4af1955b
Genetics of Atypical Parkinsonism
Stamelou, M., & Bhatia, K. P. (2015) · Springer eBooks · doi:10.1007/978-3-319-17223-1_3
- Authors
- O'Dowd, S., Curtin, D., Waite, A. J., Roberts, K., Pender, N., Reid, V., O'Connell, M., Williams, N. M., Morris, H. R., Traynor, B. J., & Lynch, T.
- Affiliations
- Mater Misericordiae University Hospital (IE)
- Cardiff University (GB)
- Beaumont Hospital (IE)
- University Hospital of Wales (GB)
- National Institutes of Health (US)
- University College Dublin (IE)
- Corresponding author
- Lynch, Timothy
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2012-07
- Volume
- 27
- Issue
- 8
- Pages
- 1072-1074
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- PMC
- PMC3516857
- OpenAlex
- W2055725404
- Cited by
- 52
- References
- 7
- Citations by year
- 2025: 1 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 8 · 2013: 14 · 2012: 2
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Institutes of Health (Z01-AG000949)
- National Institute on Aging (Z01AG000949, ZIAAG000934)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- C9orf72, GGGGCC repeat expansion, amyotrophic lateral sclerosis, frontotemporal dementia, parkinsonism
- MeSH terms
- C9orf72 Protein, Amyotrophic Lateral Sclerosis, Brain, Chromosomes, Human, Pair 9, Electromyography, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Parkinson Disease, Pedigree, Proteins, DNA Repeat Expansion, Dopamine Plasma Membrane Transport Proteins, Frontotemporal Dementia
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