Svensson P J, Anvret M, Molander M L, Nordenskjöld A
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Hum Genet. 1998 Aug;103(2):145-8. doi: 10.1007/s004390050797.
Hirschsprung disease is a congenital malformation affecting 1 in 5000 live births. The absence of parasympathetic neuronal ganglia (Meissner, Auerbach) in the hindgut results in poor coordination of peristaltic movement, and a varying degree of constipation. Four different genes have been implicated in the pathogenesis of Hirschsprung disease: the RET tyrosine kinase receptor gene; one of its ligands, the glial cell line-derived neurotrophic factor (GDNF) gene; the endothelin receptor B (EDNRB) gene; and its ligand, endothelin-3 (EDN3). Recently, combinations of mutations in two of these genes (RET and GDNF) have been reported in Hirschsprung patients. We report a family with missense mutations in both the RET gene (R982C) and the EDNRB gene (G57S). In this family, three out of five members have the two mutations, but only one, a boy, has the Hirschsprung disease phenotype. This illustrates the complexity of the molecular background of Hirschsprung disease.
先天性巨结肠是一种先天性畸形疾病，发病率为每5000例活产中有1例。后肠中副交感神经节（迈斯纳神经节、奥尔巴赫神经节）缺失导致蠕动运动协调不良，并伴有不同程度的便秘。有四种不同的基因与先天性巨结肠的发病机制有关：RET酪氨酸激酶受体基因；其配体之一，胶质细胞源性神经营养因子（GDNF）基因；内皮素受体B（EDNRB）基因；及其配体内皮素-3（EDN3）基因。最近，有报道称先天性巨结肠患者存在这两种基因（RET和GDNF）的突变组合。我们报告了一个家族，该家族的RET基因（R982C）和EDNRB基因（G57S）均存在错义突变。在这个家族中，五名成员中有三名携带这两种突变，但只有一名男孩表现出先天性巨结肠的表型。这说明了先天性巨结肠分子背景的复杂性。
