The mutational burden in os odontoideum patients

Abstract Background Os odontoideum(OO) is a rare bone malformation at the craniovertebral junction, the presence of which can lead to potential instability of atlantoaxial joints. The cause, prevalence and treatment of OO are still controversial. But the congenital factors are likely to be the main causes according to the current literature reports and the clinical characteristics of OO patients. To further explore the pathogenesis of OO, we conducted this study. Methods We consecutively recruited 25 OO patients from 2021 to 2023. The clinical manifestation and concomitant deformities were analyzed and whole-exome sequencing(WES) was performed. And the variants in OO patients were compared using genetic burden analysis with 79 normal population as controls. Results Combined with the P-value and OR value of the final data, CDC27(P = 0.002,OR = 5.08),FRG1BP(P = 0.004,OR = 5.59),TRIM8(P = 0.02,OR = 4.58) and CEP250(P = 0.005,OR = 7.78) were singled out as possible correlated gene with OO. Conclusion Our study firstly presented an exome-sequenced cohort and highlighted four novel rare variants associated with OO patients through genetic burden analysis. The results provided further evidence for potential oligogenic inheritance of OO.