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Neurobiol Aging. 2017 Mar;51:178.e11-178.e20. doi: 10.1016/j.neurobiolaging.2016.12.013. Epub 2016 Dec 21.

Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.

Author information

1
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
2
The Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
3
The Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; South East Scotland Genetics Service, Western General Hospital, Edinburgh, UK.
4
South East Scotland Genetics Service, Western General Hospital, Edinburgh, UK.
5
The Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK.
6
Institute for Genomic Medicine, Columbia University, New York, USA.
7
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
8
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. Electronic address: tim.aitman@ed.ac.uk.
9
The Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. Electronic address: siddharthan.chandran@ed.ac.uk.

Abstract

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population.

KEYWORDS:

Amyotrophic lateral sclerosis; Motor neuron disease; NEK1; TBK1

PMID:
28089114
PMCID:
PMC5302213
[Available on 2017-03-01]
DOI:
10.1016/j.neurobiolaging.2016.12.013
[Indexed for MEDLINE]
Free PMC Article

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