title: C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis.
abstract: C9orf72 hexanucleotide repeat expansions are the most common cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. The clinical presentation is often indistinguishable from classic FTD or ALS, although neuropsychiatric symptoms are more prevalent and, for ALS, behavioural and cognitive symptoms occur more frequently. Pathogenic repeat length is in the hundreds or thousands, but the minimum length that increases risk of disease, and how or whether the repeat size affects phenotype, are unclear. Like in many patients with FTD and ALS, neuronal inclusions that contain TARDBP are seen, but are not universal, and the characteristic pathological finding is of dipeptide repeat (DPR) proteins, formed by unconventional repeat-associated non-ATG translation. Possible mechanisms of neurodegeneration include loss of C9orf72 protein and function, RNA toxicity, and toxicity from the DPR proteins, but which of these is the major pathogenic mechanism is not yet certain.
authors: Dementia Research Centre, University College London (UCL) Institute of Neurology, London, UK. Electronic address: j.rohrer@ucl.ac.uk.
authors: Jonathan D
authors: JD
authors: Rohrer
authors: Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London, UK.
authors: Adrian M
authors: AM
authors: Isaacs
authors: Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London, UK.
authors: Sarah
authors: S
authors: Mizielinska
authors: MRC Prion Unit, University College London (UCL) Institute of Neurology, London, UK.
authors: Simon
authors: S
authors: Mead
authors: Queen Square Brain Bank for Neurological Disorders, University College London (UCL) Institute of Neurology, London, UK.
authors: Tammaryn
authors: T
authors: Lashley
authors: Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors: Selina
authors: S
authors: Wray
authors: Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors: Katie
authors: K
authors: Sidle
authors: Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London, UK.
authors: Pietro
authors: P
authors: Fratta
authors: Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors: Richard W
authors: RW
authors: Orrell
authors: Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
authors: John
authors: J
authors: Hardy
authors: Queen Square Brain Bank for Neurological Disorders, University College London (UCL) Institute of Neurology, London, UK.
authors: Janice
authors: J
authors: Holton
authors: Queen Square Brain Bank for Neurological Disorders, University College London (UCL) Institute of Neurology, London, UK.
authors: Tamas
authors: T
authors: Revesz
authors: Dementia Research Centre, University College London (UCL) Institute of Neurology, London, UK.
authors: Martin N
authors: MN
authors: Rossor
authors: Dementia Research Centre, University College London (UCL) Institute of Neurology, London, UK.
authors: Jason D
authors: JD
authors: Warren
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics*; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins