Continuous and Segmental Cervical Ossification of the Posterior Longitudinal Ligament Have Distinct Genomic Architectures: Inflammatory Versus Bone Metabolic Phenotypes on Whole-Exome Sequencing.

Authors

Jungbo Sim, Jun Ki Yoo, Woojin Kim, Seung Hoon Lee, Hangeul Park, Myung-Eui Seo, Ju Han Kim, Chang-Hyun Lee, Chi Heon Kim, Chun Kee Chung

Published in

Neurosurgery. Nov 09, 2026. Epub Nov 09, 2026.

Abstract

Cervical ossification of the posterior longitudinal ligament (OPLL) may represent 2 convergent entities-a genetically driven continuous phenotype and an idiopathic segmental phenotype-with a wide clinical prognosis ranging from asymptomatic to life-threatening quadriplegia. However, previous studies evaluated OPLL as a single homogeneous entity, leaving subtype-specific mechanisms unresolved. We sought to delineate the genomic, biomarker, and clinical determinants distinguishing continuous from segmental OPLL.
Patients diagnosed with cervical OPLL and healthy controls were consecutively enrolled between March 2021 and February 2024. All participants underwent whole-exome sequencing, radiological examinations, and blood biomarker measurements (C-reactive protein [CRP], white blood cell, erythrocyte sedimentation rate, alkaline phosphatase, and osteocalcin). To maximize phenotypic homogeneity, subgroups were defined by K-means clustering (occupying ratio and progression rate). Single-variant and gene-wise variant burden analyses were performed.
In total, 176 participants were enrolled: 52 with continuous/mixed OPLL (Group C), 58 with segmental/localized OPLL (Group S), and 66 OPLL-free controls (Group N). Clustering identified a severe continuous subgroup (n = 31) and a mild segmental subgroup (n = 45). Group C was significantly younger and exhibited greater ossification depth, length, and occupying ratio; faster progression; and higher white blood cell count and CRP level than Group S; the annual progression rate correlated positively with CRP (r = 0.208, P = .035). Gene-wise analysis associated the severe subgroup C with immune- and oxidative stress-related genes (KIR2DL3, OGG1), OR2T6, and ZAR1 relative to controls, whereas CCDC154, a bone metabolism gene, uniquely distinguished the segmental phenotype and displayed a graded burden that increased sequentially from the severe continuous to the milder segmental subgroups.
Continuous and segmental OPLL exhibit distinct genomic architectures-an inflammatory phenotype (KIR2DL3, OGG1) vs a bone metabolic phenotype (CCDC154). This multimodal subtyping may support a mechanism-based reclassification of OPLL and guide patient-specific prognostication.

PMID:
43001882
Bibliographic data and abstract were imported from PubMed on 09 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.