UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.

Fratta, P; Polke, JM; Newcombe, J; Mizielinska, S; Lashley, T; Poulter, M; Beck, J; ... Fisher, EM; + view all (2015) Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion. Neurobiology of Aging , 36 (1) 546.e1-546.e7. 10.1016/j.neurobiolaging.2014.07.037. Green open access

[img]
Preview
Text
devoy_anny_1-s2.0-S0197458014005065-main.pdf

Download (1MB) | Preview
[img]
Preview
Text
devoy_anny_supplementary_data.pdf

Download (1MB) | Preview

Abstract

An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0-30 hexanucleotide repeats are present in the general population, expansions >500 repeats are associated with C9ALS/FTD. Large C9ALS/FTD expansions share a common haplotype and whether these expansions derive from a single founder or occur more frequently on a predisposing haplotype is yet to be determined and is relevant to disease pathomechanisms. Furthermore, although cases carrying 50-200 repeats have been described, their role and the pathogenic threshold of the expansions remain to be identified and carry importance for diagnostics and genetic counseling. We present clinical and genetic data from a UK ALS cohort and report the detailed molecular study of an atypical somatically unstable expansion of 90 repeats. Our results across different tissues provide evidence for the pathogenicity of this repeat number by showing they can somatically expand in the central nervous system to the well characterized pathogenic range. Our results support the occurrence of multiple expansion events for C9ALS/FTD.

Type: Article
Title: Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neurobiolaging.2014.07.037
Publisher version: http://dx.doi.org/10.1016/j.neurobiolaging.2014.07...
Language: English
Additional information: Copyright ©� 2015 The Authors. Published by Elsevier Inc.This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/3.0/).
Keywords: Amyotrophic lateral sclerosis, Frontotemporal dementia, Somatic instability
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > MRC Prion Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: http://discovery.ucl.ac.uk/id/eprint/1447226
Downloads since deposit
105Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item