Identification of Novel Gene Mutations in Degenerative Lumbar Spinal Stenosis Using Whole Exome Sequencing in Chinese Population

Background Degenerative lumbar spinal stenosis (DLSS) is a common lumbar disease requiring surgery. Previous studies indicate that genetic mutation may play a part in DLSS. However, there is scarcely specific study regarding the genetic study for DLSS. Whole exome sequencing (WES) is an effective strategy to search for disease-causing genes. Methods To identify probable susceptible genes, we performed a WES in a cohort of 50 patients with DLSS and 25 controls. Raw whole exome sequencing data were filtered and mapped to human reference genome. Potential deleterious mutations were then identified by utilizing a series of bioinformatical analyses tools (PolyPhen2, SIFT, Mutation Taster, Combined Annotation Dependent Depletion (CADD), and Phenolyzer). Identified LDSS-related variants generated from the current cohort were then confirmed by compared with public database (Novegene database).Results In the current cohort, we found that the major variant classification was Missense_mutation, the major variant type was Single Nucleotide Polymorphism (SNP) and the major Single Nucleotide Variation (SNV) was C>T. Further bioinformatics analyses had successfully identified that several novel variants including HLA-DRB1, PARK2, ACTR8, AOAH, BCORL1, MKRN2, NRG4, NUP205, etc. were LDSS-related variants. Pathway enrichment analyzes revealed that those mutated genes was mainly enriched on immune response-related signaling pathways.Conclusions To the best of our knowledge, this is the first genetic study of susceptibility genes with DLSS by WES in Chinese patients. The current study revealed that deleterious mutations in several genes may contribute to the development of DLSS. Further WES studies of DLSS patients with larger number are needed to better comprehend the genetic landscape of the pathophysiology of DLSS.