A Pain in the NEK1: Differentiating Genetic Causes from Risk Factors in ALS

Since the initial description in 1993 of mutations in the superoxide dismutase (SOD1) gene as the first identified genetic cause of amyotrophic lateral sclerosis (ALS), we now recognize dozens of genes that, when mutated, may cause ALS (e.g., C9orf72). Investigators now provide compelling evidence that rare variants in the NEK1 gene are important risk factors for ALS. In an initial analysis of 1022 familial ALS patients and 7315 controls, the researchers found a greater burden of rare variants in NEK1 among patients than in controls. Independently, they identified evidence that NEK1 p.Arg261His alleles were shared by four unrelated ALS patients in an isolated Dutch community and associated this variant with sporadic ALS in a separate, multi…