Genetic and clinical characteristics of ALS patients with NEK1 gene variants

NIMA-related kinase 1(NEK1) gene was related to amyotrophic lateral sclerosis (ALS). However, genetic spectrum and clinical characteristics of ALS patients with NEK1 variants was largely unknown. We conducted genetic analysis on 1587 Chinese ALS patients and used software to predict the pathogenicity of NEK1 missense variant. We searched the literatures in PubMed, Embase, and Web of Science. In our ALS cohort, 42 ALS patients (2.6%) carried NEK1 variants, including 10 novel loss-of-function (LoF) variant carriers and 32 missense variant carriers. 90% of the NEK1 LoF variant carriers had upper limbs onset. The median survival time of LoF variant carriers tend to be shorter than that of probably pathogenic variant carriers (23.80 vs. 42.77 months). In 16 related studies, 167 different NEK1 variants, including 62 LoF and 105 missense variants, were found in 237 reported ALS patients. It was found that the survival time of LoF variant carriers was significantly shorter than that of missense variant carriers. Our study expanded the genotype and phenotype spectrum of ALS patients with NEK1 variants.