C9orf72 repeat expansions are a rare genetic cause of parkinsonism
Open accessAbstract
The recently identified C9orf72 gene accounts for a large proportion of amyotrophic lateral sclerosis and frontotemporal lobar degenerations. As several forms of these disorders are associated with parkinsonism, we hypothesized that some patients with Parkinson's disease or other forms of parkinsonism might carry pathogenic C9orf72 expansions. Therefore, we looked for C9orf72 repeat expansions in 1446 unrelated parkinsonian patients consisting of 1225 patients clinically diagnosed with Parkinson's disease, 123 with progressive supranuclear palsy, 21 with corticobasal degeneration syndrome, 43 with Lewy body dementia and 25 with multiple system atrophy-parkinsonism. Of the 1446 parkinsonian patients, five carried C9orf72 expansions: three patients with typical Parkinson's disease, one with corticobasal degeneration syndrome and another with progressive supranuclear palsy. This study shows that (i) although rare, C9orf72 repeat expansions may be associated with clinically typical Parkinson's disease and also with other parkinsonism; (ii) in several patients, parkinsonism was levodopa-responsive and remained pure, without associated dementia, for >10 years and (iii) interestingly, all C9orf72 repeat expansion carriers had positive family histories of parkinsonism, degenerative dementias or amyotrophic lateral sclerosis. This study also provides the tools for identifying parkinsonian patients with C9orf72 expansions, with important consequences for genetic counselling.
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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 [160]
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- Authors
- Lesage, S., Le Ber, I., Condroyer, C., Broussolle, E., Gabelle, A., Thobois, S., Pasquier, F., Mondon, K., Dion, P. A., Rochefort, D., Rouleau, G. A., Dürr, A., Brice, A., & for the French Parkinson’s Disease Genetics (PDG) Study Group
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- 1 Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UMR-S975; Inserm, U975, CNRS, UMR 7225, 75013 Paris, France
- Lyon 1 Université (FR)
- Hôpital Gui de Chauliac (FR)
- Hôpital Roger Salengro (FR)
- Centre Hospitalier Universitaire de Tours (FR)
- Centre Hospitalier de l’Université de Montréal (CA)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02-01
- Volume
- 136
- Issue
- 2
- Pages
- 385-391
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3984141
- OpenAlex
- W2118510420
- Cited by
- 164
- References
- 24
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 12 · 2020: 11 · 2019: 10 · 2018: 12 · 2017: 10 · 2016: 15 · 2015: 20 · 2014: 28 · 2013: 18
- FWCI
- 17.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR-08-NEUR-0004)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- C9orf72, repeat expansion, parkinsonism, Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, genetic counseling, family history (medicine), levodopa response
- MeSH terms
- C9orf72 Protein, Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Parkinson Disease, Pedigree, Proteins, Open Reading Frames, Trinucleotide Repeat Expansion, Young Adult
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