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

被引：32

作者：

Black, Holly A. ^{[1
]}

Leighton, Danielle J. ^{[2
,3
]}

Cleary, Elaine M. ^{[2
,3
,4
]}

Rose, Elaine ^{[1
]}

Stephenson, Laura ^{[2
,3
]}

Colville, Shuna ^{[2
,3
]}

Ross, David ^{[1
]}

Warner, Jon ^{[4
]}

Porteous, Mary ^{[4
]}

Gorrie, George H. ^{[2
]}

Swingler, Robert ^{[2
]}

Goldstein, David ^{[5
]}

Harms, Matthew B. ^{[5
]}

Connick, Peter ^{[3
]}

Pal, Suvankar ^{[2
,3
]}

Aitman, Timothy J.

Chandran, Siddharthan ^{[2
,3
]}

机构：

[1] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh EH8 9YL, Midlothian, Scotland

[2] Univ Edinburgh, Euan MacDonald Ctr Motor Neurone Dis Res, Edinburgh, Midlothian, Scotland

[3] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland

[4] Western Gen Hosp, South East Scotland Genet Serv, Edinburgh, Midlothian, Scotland

[5] Columbia Univ, Inst Genom Med, New York, NY USA

来源：

NEUROBIOLOGY OF AGING | 2017年 / 51卷

关键词：

Motor neuron disease; Amyotrophic lateral sclerosis; TBK1; NEK1; AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE; EL-ESCORIAL; CLINICAL CHARACTERISTICS; FRONTOTEMPORAL DEMENTIA; REPEAT EXPANSION; FAMILIAL ALS; MUTATIONS; C9ORF72; PHENOTYPE;

D O I：

10.1016/j.neurobiolaging.2016.12.013

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. (c) 2017 The Authors. Published by Elsevier Inc.

引用

页码：178.e11 / 178.e20

页数：10

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