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Lancet Neurol. 2015 Mar;14(3):291-301. doi: 10.1016/S1474-4422(14)70233-9. Epub 2015 Jan 29.

C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis.

Author information

1
Dementia Research Centre, University College London (UCL) Institute of Neurology, London, UK. Electronic address: j.rohrer@ucl.ac.uk.
2
Department of Neurodegenerative Disease, University College London (UCL) Institute of Neurology, London, UK.
3
MRC Prion Unit, University College London (UCL) Institute of Neurology, London, UK.
4
Queen Square Brain Bank for Neurological Disorders, University College London (UCL) Institute of Neurology, London, UK.
5
Department of Molecular Neuroscience, University College London (UCL) Institute of Neurology, London, UK.
6
Dementia Research Centre, University College London (UCL) Institute of Neurology, London, UK.

Erratum in

  • Lancet Neurol. 2015 Apr;14(4):350.

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.

PMID:
25638642
DOI:
10.1016/S1474-4422(14)70233-9
[Indexed for MEDLINE]

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