Genetic study of Hirschsprung's disease

(1)分析散发性巨结肠病患者中RET、EDNRB、ET-3、SOX10基因是否存在突变。(2)定量比较获得的巨结肠病患者神经节和神经节肠段RET和EDNRB基因的表达。(3)在本研究中，大约10%的患者确认了RET或EDNRB基因的致病突变，并被认为与先天性巨结肠病的病因有关。另一方面，ET-3和SOX10基因未检测到突变，这些基因突变不太可能在疾病的发展中起作用。(4) RET基因突变与长片段型相关，EDNRB基因突变与短片段型相关。(5)在一些未检测到基因突变的病例中，神经节节段的RET基因表达明显低于正常神经节节段。因此，在这些病例中，胚胎发生期间RET的消除表达可能与Hirsehsprung病的发展有关。(6)在检查病例的神经节段观察到NOS基因的表达降低，似乎解释了Hirschsprung病的主要病理生理；神经节肠过度收缩

(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.