Identification of susceptibility loci for thoracic ossification of the posterior longitudinal ligament by whole-genome sequencing

Abstract

Ossification of the posterior longitudinal ligament (OPLL) is a myelopathy commonly observed in the cervical spine. By contrast, thoracic OPLL (T-OPLL) is rare but more severe. Previous studies have identified several polymorphisms in osteogenic genes that are associated with the occurrence and development of cervical OPLL. However, few genetic studies have evaluated T-OPLL. The present study aimed to identify the genetic factors for OPLL by performing whole-genome sequencing (WGS) in 30 unrelated northern Chinese Han patients with T-OPLL. Using bioinformatics analyses and damaging-variant prediction algorithms, two deleterious variants [c.1534G>A(p.Gly512Ser)/collagen, type VI, α1 (COL6A1)] and [c.2275C>A(p.Leu759Ile)/inteleukin-17 receptor C (IL17RC)] were identified in seven unrelated patients. These two mutations resulted in markedly increased gene expression levels in peripheral blood samples. To the best of our knowledge, this is the first report to describe the use of WGS analysis of T-OPLL in the northern Chinese Han population. The results revealed two novel potentially pathogenic mutations in patients with T-OPLL.