Objective To explore the efficacy of blood promoter methylation of Sox10 gene in diagnosis of intestinal neuronal dysplasia (IND) and to seek a non-invasive genetic diagnosis method based on peripheral blood for diagnosis of IND.Methods Children diagnosed as Hirschsprung disease (HD) or IND from the Shengjing Hospital of China Medical University and the Capital Institute of Pediatrics were enrolled in 2017-2018.The blood and colon specimens were collected from 9 IND,15 HD and 15 controls (the colon trauma cases).The blood promoter methylation of Soxl0 and its expression level in colon were both detected and the correlation between them was analyzed.The diagnostic efficacy of blood promoter methylation of Soxl0 was analyzed by receiver operating characteristics (ROC) curve.Results The blood promoter methylation level at the 32nd locus of Sox10 was 100％ (90％-100％;95％ CI:91％-98％) in the control,80％ (70％-90％;95％CI:65％-90％) in HD and 60％ (50％-80％;95％ CI:52％-82％) in IND.The expression level of Sox10 in the colon was (1.00 ±0.04) in the control,(2.75 ±0.16) in HD and (3.99 ±0.10) in IND.Western blot showed that the expression of Sox10 protein in the colon of the control group,the HD group and the IND group increased,and the difference was statistically significant (P ＜ 0.05).The blood promoter methylation level was negatively correlated with its expression level in colon (r =-0.88).ROC curve indicated area under curve (AUC) of Sox10 methylation in diagnosis of HD was 0.818,with a cut-off value of 85％ and low diagnostic sensitivity.The AUC in IND was 0.907,with a cut-off value of 85％,producing a sensitivity of 88.9％ and a specificity of 93.3％ respectively.Conclusion Blood promoter methylation of Sox10 might be used as a non-invasive method for diagnosis of IND.

The enteric nervous system consists of a network of neurons,neurotransmitters,proteins and its supporting cells in the lining of the gastrointestinal wall. The embryonic development of ENS originates from neural crest stem cells,which start to proliferate and migrate from the neural crest to the mesoderm along the head and tail,and finally migrate into the mesenchyme and form ENS. DNA methylation plays an important role in cell proliferation or differentiation in the process of embryonic development. DNA methylation is regulated by DNA methylation transferase,and the methylation state of the genes is passed on to the offspring in the process of cell proliferation differentiation. DNA methylation is the most profound and extensive mechanism in epigenet-ics research. Thus,this article is to review the recent advances in the effects of epigenetic regulation on the devel-opment of the enteric nervous system.