NEK1 genetic variability in a Belgian cohort of ALS and ALS-FTD patients

Neurobiol Aging. 2018 Jan;61:255.e1-255.e7. doi: 10.1016/j.neurobiolaging.2017.08.021. Epub 2017 Aug 31.


We evaluated the genetic impact of the amyotrophic lateral sclerosis (ALS) risk gene never in mitosis gene a-related kinase 1 (NEK1) in a Belgian cohort of 278 patients with ALS (n = 245) or ALS with frontotemporal dementia (ALS-FTD, n = 33) and 609 control individuals. We identified 2 ALS patients carrying a loss-of-function (LOF) mutation, p.Leu854Tyrfs*2 and p.Tyr871Valfs*17, that was absent in the control group. A third LOF variant p.Ser1036* was present in 2 sibs with familial ALS but also in an unrelated control person. Missense variants were common in both patients (3.6%) and controls (3.0%). The missense variant, p.Arg261His, which was previously associated with ALS risk, was detected with a minor allele frequency of 0.90% in patients compared to 0.33% in controls. Taken together, NEK1 LOF variants accounted for 1.1% of patients, although interpretation of pathogenicity and penetrance is complicated by the observation of occasional LOF variants in unaffected individuals (0.16%). Furthermore, enrichment of additional ALS gene mutations was observed in NEK1 carriers, suggestive of a "second hit" model were NEK1 variants may modify disease presentation of driving mutations.

Keywords: Amyotrophic lateral sclerosis (ALS); Frontotemporal dementia (FTD); NEK1; NIMA-related kinase 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Belgium
  • Cohort Studies
  • Female
  • Frontotemporal Dementia / genetics*
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Variation / genetics*
  • Humans
  • Loss of Function Mutation / genetics*
  • Male
  • Middle Aged
  • NIMA-Related Kinase 1 / genetics*
  • Risk


  • NEK1 protein, human
  • NIMA-Related Kinase 1

Supplementary concepts

  • Frontotemporal Dementia With Motor Neuron Disease