Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.
Genetic epidemiology of motor neuron disease-associated variants in the Scottish population.
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DOI：
10.1016/j.neurobiolaging.2016.12.013
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发表时间：
2017-03
影响因子：
4.2
通讯作者：
Chandran S
中科院分区：
文献类型：
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作者：
Black HA;Leighton DJ;Cleary EM;Rose E;Stephenson L;Colville S;Ross D;Warner J;Porteous M;Gorrie GH;Swingler R;Goldstein D;Harms MB;Connick P;Pal S;Aitman TJ;Chandran S
运动神经元病（MND）的遗传学理解在过去10年中有了很大的发展，包括最近确定的MND与TBK1和NEK1变异之间的关联。我们的目的是确定已知MND基因中致病性变异的频率，并评估TBK1和NEK1的变异是否有助于苏格兰人群中MND的负担。在441例病例和400例对照中进行了SOD1、TARDBP、OPTN、TBK1和NEK1的测序。除了44例已知携带C9orf72六核苷酸重复扩增的病例外，我们还确定了31例病例和2例对照携带功能丧失或致病性变异。在TBK1中发现3例病例的功能丧失变异体，而在对照中没有发现，在NEK1中分别发现3例病例的功能丧失变异体，而在对照中没有发现。这项研究提供了一个准确的描述MND在苏格兰的遗传流行病学和TBK1和NEK1的MND易感性在苏格兰人口的贡献提供了支持。
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.
影响因子：
--
作者：
Kerr SM;Liewald DC;Campbell A;Taylor K;Wild SH;Newby D;Turner M;Porteous DJ
通讯作者：
Porteous DJ