Whole Exome Sequencing in Patients With Ossification of the Spinal Ligaments

Abstract Background The clinical presentations of ossification of spinal ligament (OSL) are majorly myelopathy and/or radiculopathy, with serious neurological pathology resulting in paralysis of extremities and disturbances of motility (motor function) lowering the quality of life. Currently, studies find that missense single nucleotide polymorphisms (SNPs) play a vital role in the susceptibility for complex diseases. Methods In the present study, we used whole exome sequencing (WES) method to explore variants in exomes and found out novel potential responsible genes for OSL. Genomic DNA was extracted from ligamentum flavum collected from 5 OSL patients and 5 control patients. Whole-exome sequencing was then performed, while variation forecasts and conservation examination were subsequently assessed. Results 8 common SNP variants were exhibited in all 5 subjects of OSL, presented in the genes of GRHL2, CUL3, WHAMM, IL17RD, POM121L12, SLC26A8 and PTPN23. After screened with numbers of samples and additional screenings with deleterious Polyphen2_HDIV_score, Polyphen2_HVAR_score and SIFT, 4 common SNP variants were displayed in 4 subjects of OSL, presented in the genes of KRT84, KIF1B, NRAP and CETN1. 7 common SNP variants were existed in 3 subjects of OSL, presented in the genes of CCT3, ANLN, ESRRB, SRBD1, ODF3L1, BRAT1 and RBP3. Conclusion We found out novel potential variants in several genes, especially WHAMM, KIF1B and ESRRB, which represented potentially pathogenic mutations in patients with OSL.