Liu Gang, Zhao Hengqiang, Yan Zihui, Zhao Sen, Niu Yuchen, Li Xiaoxin, Wang Shengru, Yang Yang, Liu Sen, Zhang Terry Jianguo, Wu Zhihong, Wu Nan
Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Mol Ther Nucleic Acids. 2021 Feb 10;23:1281-1287. doi: 10.1016/j.omtn.2021.02.002. eCollection 2021 Mar 5.
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 that 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 was 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 the mitogen-activated protein kinase (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 , , , , and and hypo DMR-related genes, including , , , , and , may contribute to the pathogenesis of hemivertebra. The aberrant DNA methylation may be associated with the formation of hemivertebra and congenital scoliosis.
先天性脊柱侧凸（CS）是一种由椎骨畸形引起的先天性疾病。最近的研究表明，DNA修饰可能与疾病的发病机制有关。本研究旨在确定可能与CS发病机制有关的表观遗传扰动。招募了4例患有半椎体的CS患者并接受了脊柱矫正手术。在半椎体切除过程中，从标本中收集半椎体和棘突并提取DNA。使用全基因组亚硫酸氢盐测序（WGBS）在碱基对分辨率下检查全基因组DNA甲基化谱。我们分别鉴定出343个具有高差异甲基化区域（DMR）的基因和222个具有低DMR的基因。这些基因在京都基因与基因组百科全书（KEGG）途径的丝裂原活化蛋白激酶（MAPK）信号通路、钙信号通路和轴突导向中富集，并且在基因本体生物学过程（GO-BP）术语的参与分化的细胞形态发生的正调控、参与分化的细胞形态发生的调控以及神经元投射发育的调控中富集。与高DMR相关的基因，包括……以及与低DMR相关的基因，包括……，可能与半椎体的发病机制有关。异常的DNA甲基化可能与半椎体的形成和先天性脊柱侧凸有关。
