title: Analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism.
abstract: A GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia. There is suggestion that these expansions may be a rare cause of parkinsonian disorders such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). Screening the C9orf72 gene in 37 patients with features of corticobasal syndrome (CBS) detected an expansion in 3 patients, confirmed by Southern blotting. In a series of 22 patients with clinically diagnosed PSP, we found 1 patient with an intermediate repeat length. We also screened for the C9orf72 expansion in a large series of neuropathologically confirmed samples with MSA (n = 96), PSP (n = 177), and CBD (n = 18). Patients were found with no more than 22 GGGGCC repeats. Although these results still need to be confirmed in a larger cohort of CBS and/or CBD patients, these data suggest that in the presence of a family history and/or motor neuron disease features, patients with CBS or clinical PSP should be screened for the C9orf72 repeat expansion. In addition, we confirm that the C9orf72 expansions are not associated with pathologically confirmed MSA, PSP, or CBD in a large series of cases.
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Lucia V
authors.initials: LV
authors.lastname: Schottlaender
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Neurogenetics Laboratory, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Polke
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Reta Lila Weston Institute for Neurological Studies, The Queen Square Brain Bank, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Ling
authors.affiliation: The MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Nicola D
authors.initials: ND
authors.lastname: MacDoanld
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Arianna
authors.initials: A
authors.lastname: Tucci
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Neurogenetics Laboratory, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Tina
authors.initials: T
authors.lastname: Nanji
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Reta Lila Weston Institute for Neurological Studies, The Queen Square Brain Bank, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Pittman
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Reta Lila Weston Institute for Neurological Studies, The Queen Square Brain Bank, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Reta Lila Weston Institute for Neurological Studies, The Queen Square Brain Bank, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Reta Lila Weston Institute for Neurological Studies, The Queen Square Brain Bank, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Neurogenetics Laboratory, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Sweeney
authors.affiliation: Laboratory of Neurogenetics, NIA, NIH, Bethesda, MD, USA.
authors.forename: Andy B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Reta Lila Weston Institute for Neurological Studies, The Queen Square Brain Bank, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.affiliation: The Sobell Department of Movement Disorders, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; Neurogenetics Laboratory, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK; The MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK. Electronic address: h.houlden@ucl.ac.uk.
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
mesh_terms: D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000235:genetics; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics; D013577:Syndrome
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: C9orf72; Corticobasal degeneration (CBD) and corticobasal syndrome (CBS); Multiple system atrophy (MSA); Parkinsonism; Progressive supranuclear palsy (PSP)