Objective NIMA-related kinase 1 ( NEK1 ) have been implicated in amyotrophic lateral sclerosis (ALS). But genetic spectrum and clinical presentation have not been systematically defined. Methods We screened 378 ALS patients and identified NEK1 variant carriers. Clinical records were reviewed retrospectively to characterise phenotypes. Leukocytes were isolated after routine testing and NEK1 protein abundance was quantified by western blot to assess the relationship between NEK1 protein levels and the rate of clinical progression. In parallel, we conducted a structured narrative review of published NEK1 -ALS cases based on a systematic search of PubMed, Embase, and Web of Science. We extracted genetic and clinical information to summarise the variant spectrum, co-mutation profiles, and phenotype differences across populations. Results NEK1 variants were identified in 8 of 378 patients (2.12%). Protein analysis showed lower peripheral NEK1 levels among carriers than among controls in this small exploratory sample. An exploratory analysis further suggested that lower systemic NEK1 protein levels may be associated with faster disease progression; however, because these measurements were obtained from peripheral leukocytes at highly heterogeneous sampling times and without adjustment for major clinical confounders, they should be interpreted strictly as descriptive observations and do not support biomarker claims. While phenotypic heterogeneity and population-specific variant distributions were observed, these findings remain descriptive due to the small sample size. Conclusion This regional case series provides a descriptive overview of NEK1 variants in a Chinese ALS cohort and offers preliminary exploratory evidence consistent with reduced peripheral NEK1 protein levels in variant carriers. The observed inverse relationship between lower measured protein levels and faster clinical decline should be regarded as hypothesis-generating only. Given the small sample size, highly heterogeneous sampling times, use of peripheral leukocytes, and lack of adjustment for major clinical confounders, these protein data do not support biomarker claims at this stage. Validation in larger, prospective multi-center cohorts with standardized longitudinal sampling is required.
Chen et al. (Thu,) studied this question.