Vega Hernández L, Castaño González L, Belar Beitia O, Ruíz Aja E, Martínez Ezquerra N, López Alvarez-Buhilla P
Unidad de Investigación, Hospital de Cruces, Barakaldo, Bizkaia.
Cir Pediatr. 2011 Aug;24(3):131-6.
Hirschsprung's disease (HSCR) is a developmental disorder characterised by the absence of the enteric ganglia along the intestine. Is regarded as the consequence of the premature arrest of the migration of neural crest cells in the hindgut during the embryonic development to form the enteric nervous system (ENS). Is considered, therefore, a neurocristopathy. The development of surgical approaches has importantly decreased mortality and morbility of Hirschsprung's patients, which has allowed the emergence of genetic studies of patients and their families. Although the genetic cause of the disease is still unknown, the RET oncogene is the main involved. Alterations in this gene have been found in HSCR patients, so many authors suggest that certain polymorphisms (SNPs) in this gene could be responsible of genetic predisposition to have the disease. Our work has consisted in the genetic analysis of the RET gene in HSCR patients using direct sequencing and genotyping with TaqMan probes. Our results show that some alleles of the polymorphisms p.Leu769Leu (c.2307T>G, Exon 13) p.Gly691Ser (c.2071G>A, Exon 11) and p.Ser904Ser (c.2712C>G, Exon 15) are associated to the disease since there are significant differences from the healthy population.
先天性巨结肠症（HSCR）是一种发育障碍性疾病，其特征是肠道沿线缺乏肠神经节。它被认为是胚胎发育过程中后肠神经嵴细胞迁移过早停滞，无法形成肠神经系统（ENS）的结果。因此，它被视为一种神经嵴病。手术方法的发展显著降低了先天性巨结肠症患者的死亡率和发病率，这使得对患者及其家族的遗传学研究得以开展。尽管该疾病的遗传病因仍不清楚，但RET原癌基因是主要相关因素。在先天性巨结肠症患者中已发现该基因的改变，因此许多作者认为该基因中的某些多态性（单核苷酸多态性，SNPs）可能是导致该病遗传易感性的原因。我们的工作包括使用直接测序和TaqMan探针基因分型对先天性巨结肠症患者的RET基因进行遗传分析。我们的结果表明，多态性p.Leu769Leu（c.2307T>G，第13外显子）、p.Gly691Ser（c.2071G>A，第11外显子）和p.Ser904Ser（c.2712C>G，第15外显子）的某些等位基因与该疾病相关，因为与健康人群存在显著差异。
