The developmental genetics of Hirschsprung's disease
The developmental genetics of Hirschsprung's disease
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DOI：
10.1111/cge.12032
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发表时间：
2013-01-01
影响因子：
3.5
通讯作者：
Pilon, N.
中科院分区：
文献类型：
--
作者：
Bergeron, K-F;Silversides, D. W.;Pilon, N.
贝杰隆·K-F，Silverside DW，Pilon N.先天性巨结肠的发育遗传学.临床基因2013：83：15-22。(C)John Wiley&Sons A/S由Blackwell出版有限公司出版，2012年先天性巨结肠(HSCR)，又称无神经节细胞巨结肠，源于肠道神经系统(ENS)的先天性畸形。报告显示，每5000名活产儿中就有一名，男女性别比为4：1。临床症状包括严重便秘和因结肠不能活动而引起的肠胀。如果不治疗，无神经节细胞的巨结肠是致命的。这种严重的先天性疾病是由于缺乏结肠神经节，从而缺乏结肠的内在神经，而这又是由于ENS前体细胞对发育中的肠道的不当定植所致。这些祖细胞来源于一种称为神经脊细胞(NCC)的瞬时干细胞群体。HSCR的遗传学是复杂的，可能涉及多个基因的突变。然而，据估计，已知基因突变在临床观察到的HSCR病例中所占比例不到一半。男性的性别偏见目前还没有得到解释。这篇综述的目的是在我们对NCC发育、性染色体遗传学和实验室模型的现有知识的背景下，提供关于HSCR的病理生理学和遗传学的概述。
Bergeron K-F, Silversides DW, Pilon N. The developmental genetics of Hirschsprung's disease. Clin Genet 2013: 83: 15-22. (C) John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2012 Hirschsprung's disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). It displays an incidence of 1 in 5000 live births with a 4: 1 male to female sex ratio. Clinical signs include severe constipation and distended bowel due to a non-motile colon. If left untreated, aganglionic megacolon is lethal. This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells. These progenitor cells are derived from a transient stem cell population called neural crest cells (NCC). The genetics of HSCR is complex and can involve mutations in multiple genes. However, it is estimated that mutations in known genes account for less than half of the cases of HSCR observed clinically. The male sex bias is currently unexplained. The objective of this review is to provide an overview of the pathophysiology and genetics of HSCR, within the context of our current knowledge of NCC development, sex chromosome genetics and laboratory models.