title: Multiple system atrophy is not caused by C9orf72 hexanucleotide repeat expansions.
abstract: Multiple system atrophy (MSA) is a fatal neurodegenerative disorder of unknown etiology that presents with variable combinations of progressive ataxia, parkinsonism, and autonomic instability. Pathologic expansion of a hexanucleotide repeat in the C9orf72 gene has been demonstrated to cause neurodegeneration with diverse neurologic presentations. To test the hypothesis whether pathologic expansions in C9orf72 are a cause of MSA, we undertook genetic screening in 100 neuropathologically confirmed cases. No pathologic repeat expansions were detected suggesting that MSA is not a C9orf72-related neurodegenerative disease.
authors.affiliation: Department of Neurology, Johns Hopkins Hospital, Baltimore, MD, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. Electronic address: sscholz5@jhmi.edu.
authors.forename: Sonja W
authors.initials: SW
authors.lastname: Scholz
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Majounie
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK.
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.affiliation: UF Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, Department of Neurology, Gainesville, FL, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Laboratories, UCL Institute of Neurology, London, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000073885:C9orf72 Protein; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D019578:Multiple System Atrophy / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: Amyotrophic lateral sclerosis; C9orf72; Fronto-temporal dementia; Multiple system atrophy; Neurodegeneration