Ivanchuk S M, Myers S M, Eng C, Mulligan L M
Department of Pathology, Queen's University, Kingston, ON, Canada.
Hum Mol Genet. 1996 Dec;5(12):2023-6. doi: 10.1093/hmg/5.12.2023.
Hirschsprung disease (HSCR) is a common congenital abnormality characterized by absence of the enteric ganglia in the hind gut. In 10-40% of HSCR cases, mutations of the RET receptor tyrosine kinase have been found. The recent identification of a multimeric RET ligand/receptor complex suggested that mutations of genes encoding other components of this complex might also occur in HSCR. To investigate this role, we examined the gene for glial cell line-derived neurotrophic factor (GDNF), the circulating ligand of the RET receptor complex, for mutations in a panel of sporadic and familial HSCR. We identified GDNF sequence variants in 2/36 HSCR patients. The first of these was a conservative change which did not affect the GDNF protein sequence. The second variant was a de novo missense mutation in a family with no history of HSCR and without mutation of the RET gene. Thus, our data are consistent with a causative role for GDNF mutations in some HSCR cases.
先天性巨结肠症（HSCR）是一种常见的先天性异常疾病，其特征是后肠中缺乏肠神经节。在10%至40%的HSCR病例中，已发现RET受体酪氨酸激酶发生突变。最近对一种多聚体RET配体/受体复合物的鉴定表明，编码该复合物其他成分的基因也可能在HSCR中发生突变。为了研究这一作用，我们在一组散发性和家族性HSCR病例中检测了胶质细胞源性神经营养因子（GDNF）基因（RET受体复合物的循环配体）是否存在突变。我们在36例HSCR患者中发现了2例GDNF序列变异。其中第一例是保守性变化，不影响GDNF蛋白序列。第二例变异是一个无HSCR病史且RET基因无突变的家族中的新生错义突变。因此，我们的数据与GDNF突变在某些HSCR病例中的致病作用一致。
