Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative 
disease involving the upper and lower motor neurons of the spinal cord, 
brainstem, and cerebral cortex. At least 30 genes have been implicated in 
familial ALS (fALS) and sporadic ALS (sALS). Kaneb et al. (2015) first carried 
out a large-scale sequencing study in ALS patients and identified two 
loss-of-function (LOF) variants in the GLE1 gene. The LOF mutation-induced 
disruption of RNA metabolism through the haploinsufficiency mechanism is 
implicated in ALS pathogenesis. A total of 628 ALS patients and 522 individuals 
without neurodegenerative disorders were enrolled in this study to explore the 
GLE1 gene contribution to ALS in the Chinese population. All 16 exons and the 
flanking intron of GLE1 were screened by Sanger sequencing. In total, we 
identified seven rare GLE1 coding variants, including one novel nonsense 
mutation and six rare missense mutations in 628 ALS patients. The frequency of 
GLE1 LOF mutations was 0.16% (1/628) among Chinese sALS patients, implying that 
it is an uncommon genetic determinant of ALS in Chinese patients. Additionally, 
the rare missense variants in the hCG1-binding domain of GLE1 impairing the 
distribution of the hGle1B isoform at the nuclear pore complex (NPC) region may 
be involved in the pathogenesis of ALS.