title: C9orf72 repeat expansions are a rare genetic cause of parkinsonism.
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.
authors: 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
authors: Suzanne
authors: S
authors: Lesage
authors: Isabelle
authors: I
authors: Le Ber
authors: Christel
authors: C
authors: Condroyer
authors: Emmanuel
authors: E
authors: Broussolle
authors: Audrey
authors: A
authors: Gabelle
authors: Stéphane
authors: S
authors: Thobois
authors: Florence
authors: F
authors: Pasquier
authors: Karl
authors: K
authors: Mondon
authors: Patrick A
authors: PA
authors: Dion
authors: Daniel
authors: D
authors: Rochefort
authors: Guy A
authors: GA
authors: Rouleau
authors: Alexandra
authors: A
authors: Dürr
authors: Alexis
authors: A
authors: Brice
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000073885:C9orf72 Protein; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames / Q000235:genetics*; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D055815:Young Adult
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins