Loss-of-function variants in NEK1 are associated with an increased risk of sporadic ALS in the Japanese population
Loss-of-function variants in NEK1 are associated with an increased risk of sporadic ALS in the Japanese population
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DOI：
10.1038/s10038-020-00830-9
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发表时间：
2020-09
影响因子：
3.5
通讯作者：
H. Naruse;H. Ishiura;J. Mitsui;Yuji Takahashi;T. Matsukawa;J. Yoshimura;K. Doi;S. Morishita;
中科院分区：
文献类型：
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作者：
H. Naruse;H. Ishiura;J. Mitsui;Yuji Takahashi;T. Matsukawa;J. Yoshimura;K. Doi;S. Morishita;
NEK 1的功能丧失（LoF）变异体最近被报道与肌萎缩侧索硬化（ALS）有关。在这项研究中，我们调查了NEK 1 LoF变异与散发性ALS（SALS）风险增加的相关性，以及日本病例系列中携带LoF变异的SALS患者的临床特征。对446例家族性ALS致病基因的致病性变异尚未确定的SALS患者和1163例日本健康对照受试者进行全外显子组测序分析。我们评估了LoF变体，定义为无义，剪接位点破坏单核苷酸变体（SNV），或预测导致NEK 1移码的短插入/缺失（indel）变体。我们在SALS患者中发现了7种NEK 1 LoF变异（1.57%），而在对照组中仅发现了1种（0.086%）（P= 0.00073，Fisher精确检验）。这一结论与世界其他地区最近报告的结论一致。总之，我们证明了NEK 1 LoF变异也与日本人群SALS风险增加相关。
Loss-of-function (LoF) variants inNEK1have recently been reported to be associated with amyotrophic lateral sclerosis (ALS). In this study, we investigated the association ofNEK1LoF variants with an increased risk of sporadic ALS (SALS) and the clinical characteristics of patients with SALS carrying LoF variants in a Japanese case series. Whole-exome sequencing analysis was performed for a series of 446 SALS patients in whom pathogenic variants in familial ALS-causative genes have not been identified and 1163 healthy control subjects in our Japanese series. We evaluated LoF variants, defined as nonsense, splice-site disrupting single-nucleotide variants (SNVs), or short insertion/deletion (indel) variants predicted to cause frameshifts inNEK1. We identified sevenNEK1LoF variants in patients with SALS (1.57%), whereas only one was identified in control subjects (0.086%) (P= 0.00073, Fisher’s exact test). This finding is consistent with those in recent reports from other regions in the world. In conclusion, we demonstrated thatNEK1LoF variants are also associated with an increased risk of SALS in the Japanese population.