C9orf72 repeat expansions are a rare genetic cause of parkinsonism.: C9ORF72 repeat expansion in parkinsonism

Suzanne Lesage 1 Isabelle Le Ber 2 Christel Condroyer 1 Emmanuel Broussolle 3 Audrey Gabelle 4 Stéphane Thobois 3 Florence Pasquier 5 Karl Mondon 6 Patrick Dion 7 Daniel Rochefort 8 Guy Rouleau 9 Alexandra Dürr 10 Alexis Brice 11, 12, *
* Corresponding author
1 INSERM UMR_S975
CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
2 INSERM UMR_S975
CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Centre de référence sur les démences rares et maladie de Pick
10 INSERM UMR_S975
Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
Abstract : 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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Suzanne Lesage, Isabelle Le Ber, Christel Condroyer, Emmanuel Broussolle, Audrey Gabelle, et al.. C9orf72 repeat expansions are a rare genetic cause of parkinsonism.: C9ORF72 repeat expansion in parkinsonism. Brain - A Journal of Neurology , Oxford University Press (OUP), 2013, 136 (Pt 2), pp.385-91. ⟨10.1093/brain/aws357⟩. ⟨inserm-00807422⟩

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