Ossification of the posterior longitudinal ligament (OPLL) in the cervical spine is known as a rare, complex genetic disease, its complexity being partly because OPLL is diagnosed by radiological findings regardless of clinical or genetic evaluations. Although many genes associated with susceptibility have been reported, the exact causative genes are still unknown.
We performed an analysis using next-generation sequencing and including only patients with a clear involved phenotype.
This was a case control study.
A total of 74 patients with severe OPLL and 26 healthy controls were included.
Causal single-nucleotide variant (SNV), gene-wise variant burden (GVB), and related pathway METHOD: We consecutively included the severe OPLL patients with continuous-/mixed-type and an occupying ratio of ≥ 40%, and performed whole-exome sequencing (WES) and bioinformatic analysis. Then, a validation test was performed for candidate variations. Participants were divided into four groups (rapidly-growing OPLL, growing rate ≥ 2.5%/year; slow-growing, < 2.5%/year; uncertain; and control).
WES was performed on samples from 74 patients with OPLL (rapidly-growing, 33 patients; slow-growing, 37; and uncertain, 4) with 26 healthy controls. Analysis of 100 participants identified a newly implicated SNV and four candidate genes based on GVB. The GVB of CYP4B1 showed a more deleterious score in the OPLL than the control group. Comparison between the rapidly growing OPLL and control groups revealed seven newly identified SNVs. We found significant association for two rare missense variants; rs121502220 (odds ratio [OR] = infinite; minor allele frequency [MAF] = 0.034) in NLRP1 and rs13980628 (OR= infinite; MAF = 0.032) in SSH2. The three genes are associated with inflammation control and arthritis, and SSH2 and NLRP1are also related to vitamin D modulation.
Identification of unique variants in novel genes such as NLRP1, SSH2, and CYP4B1 suggests that auto-inflammation may play a role in the development and progression of OPLL.

Copyright © 2021. Published by Elsevier Inc.