Whole-genome methylation analysis of hemivertebra and spinal process tissues reveals novel epigenetic perturbation contributing to the pathogenesis of congenital scoliosis

Abstract Congenital scoliosis (CS) is a congenital disease caused by malformations of vertebrae. Recent studies demonstrated that DNA modification could contribute to the pathogenesis of disease. This study aims to identify epigenetic perturbations which may contribute to the pathogenesis of CS. Four CS patients with hemivertebra were enrolled and underwent spine correction operations. DNA was extracted from the hemivertebrae and spinal process collected from the specimen during the hemivertebra resection. Genome-wide DNA methylation profiling were examined at base-pair resolution using whole genome bisulfite sequencing (WGBS). We identified 343 genes with hyper differentially methylated regions (DMRs) and 222 genes with hypo DMRs respectively. These genes were enriched in MAPK signaling pathway, calcium signaling pathway, and axon guidance in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and were enriched in positive regulation of cell morphogenesis involved in differentiation, regulation of cell morphogenesis involved in differentiation, and regulation of neuron projection development in Biological Process of Gene Ontology (GO-BP) terms. Hyper DMR-related genes including IGHG1, IGHM, IGHG3, RNF213, GSE1, and hypo DMR-related genes including SORCS2, COL5A1, GRID1, RGS3, ROBO2 may contribute to the pathogenesis of hemivertebra. The aberrant DNA methylation may be associated with the formation of hemivertebrae and congenital scoliosis.