Genetic study of Hirschsprung's disease

(1)在散发性先天性巨结肠患者中分析RET、EDNRB、ET-3和SOX 10基因突变的可能存在。(2)RET和EDNRB基因的表达进行了定量和比较，在神经节和无神经节肠段获得的先天性巨结肠症患者。(3)在目前的研究中，RET或EDNRB基因的致病突变在大约10%的患者中得到证实，并被认为与先天性巨结肠的病因学有关。另一方面，在ET-3和SOX 10基因中没有检测到突变，这些基因突变不太可能在疾病的发展中起作用。(4)RET基因的突变似乎与长片段类型相关，而EDNRB的突变似乎与短片段类型相关。(5)在几例未检测到基因突变的病例中，RET基因在无神经节段的表达明显低于正常神经节段。因此，在这些病例中，胚胎发育过程中RET表达的缺失可能与先天性巨结肠的发生有关。(6)NOS基因的表达减少，在无神经节段的检查病例中观察到的，似乎解释了主要的病理生理学的先天性巨结肠症，过度收缩的无神经节肠。

(1) Possible existence of mutations of the RET, EDNRB, ET-3, and SOX10 genes were analyzed in sporadic patients with Hirschsprung's disease.(2) Expression of the RET and EDNRB genes were quantified and compared in both ganglionic and aganglionic bowel segments obtained Hirschsprung's disease patients.(3) Disease causative mutations of the RET or EDNRB genes were confirmed approximately in 10% of the patients in the current study, and considered to be associated with the etiology of Hirschsprung's disease. On the other hand, no mutations were detected in the ET-3 and SOX10 genes, and it is unlikely that these gene mutations have a role in the development of the disease.(4) Mutations of the RET gene seemed to be associated with long segment type, while these of the EDNRB seemed to be associated with short segment type.(5) In several cases in whom no gene mutations were detected, RET gene expression in the aganglionic segment were apparently lower than that in the normal ganglionic segment. Therefore, it is likely that abolish expression of RET during embryogenesis may be associated with the development of Hirsehsprung's disease in these cases.(6) Decreased expression of NOS gene observed in the aganglionic segments of examined cases seemed to explain the principal pathophysiology of Hirschsprung's disease ; excessive contraction of the aganglionic bowels.