Mutation screening of NEK1 in Chinese ALS patients.

NEK1 was recently identified as an amyotrophic lateral sclerosis (ALS) gene through rare variant burden analysis, and its role in ALS in various populations is still unclear. The aim of this study was to determine the frequency and spectrum of NEK1 mutations in an ALS cohort from mainland China. All exons and their flanking intron regions of NEK1 were screened by direct nucleotide sequencing in 377 unrelated ALS patients. These patients were also screened with a massive parallel sequencing gene panel for 24 known ALS genes and C9orf72 hexanucleotide repeat expansion. In totality, we detected 9 variants, comprising 3 novel heterozygous loss-of-function mutations and 6 rare missense variants (MAF < 0.1%) in NEK1. The patient with splice site mutation also carried another probably damaging variant in SOD1. Our study established a NEK1 mutant frequency of 0.8% in Chinese ALS patients, further expanded its spectrum of variants, and highlighted the possibility of coexistence with variants in additional ALS genes in NEK1 loss-of-function carriers.