Loss-of-function variants in NEK1 are associated with an increased risk of sporadic ALS in the Japanese population.

Autor: Naruse H; Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Ishiura H; Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Mitsui J; Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Takahashi Y; Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan., Matsukawa T; Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Yoshimura J; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan., Doi K; School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan., Morishita S; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan., Goto J; Department of Neurology, International University of Health and Welfare Mita Hospital, Tokyo, Japan., Toda T; Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Tsuji S; Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. tsuji@m.u-tokyo.ac.jp.; Institute of Medical Genomics, International University of Health and Welfare, Chiba, Japan. tsuji@m.u-tokyo.ac.jp.
Jazyk: angličtina
Zdroj: Journal of human genetics [J Hum Genet] 2021 Mar; Vol. 66 (3), pp. 237-241. Date of Electronic Publication: 2020 Sep 12.
DOI: 10.1038/s10038-020-00830-9
Abstrakt: Loss-of-function (LoF) variants in NEK1 have recently been reported to be associated with amyotrophic lateral sclerosis (ALS). In this study, we investigated the association of NEK1 LoF 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 in NEK1. We identified seven NEK1 LoF 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 that NEK1 LoF variants are also associated with an increased risk of SALS in the Japanese population.
Databáze: MEDLINE
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