Identification of potential pathogenic genes causing occipitalization of the atlas

Abstract Background Occipitalization of the atlas (AO) is among the most common congenital or environmental malformations of the craniovertebral region, the rate of incidence of which ranges from 0.08%-2.76% in the general population. The fundamental pathogenic mechanisms and molecular etiology remain largely unknown.. Results Rare variants were detected in two genes (MEOX1 and MYO18B) with reported association with vertebral malformations, especially in AO. Through the use of a functional prediction tool, Meta-SVM, and genotype-phenotype analysis of 101 candidate genes related to vertebral segmentation abnormalities, TNS1 was identified as having the greatest probability of being associated with AO, followed by FGFR2, AGAP1, TBX2, LRP5, and TONSL. GO-BP and KEGG analyses were then performed on the candidate genes, the results indicating that Fanconi anemia-related genes may drive vertebral malformation in AO patients.. Conclusions The present study analyzed the WES profile of a cohort of Chinese AO patients and identified 6 novel genes potentially associated with AO, extending the spectrum of known mutants contributing to this disorder. Furthermore, functional gene enrichment analysis provided fresh insight into the Fanconi anemia related pathway and etiology of AO.