RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects
RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects
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DOI：
10.1136/jmg.2010.088526
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发表时间：
2011-07-01
影响因子：
4
通讯作者：
Salomon, Remi
中科院分区：
文献类型：
--
作者：
Jeanpierre, Cecile;Mace, Guillaume;Salomon, Remi
RET/GDNF信号通路在肾脏和肠神经系统的发育过程中起着至关重要的作用。在人类中，RET激活突变导致多发性内分泌瘤，而失活突变导致巨结肠病。根据对一小部分样本的分析，在肾发育不全的胎儿中也有RET突变的报道。目的和方法为了更好地描述RET和GDNF在肾脏发育缺陷中的作用，我们对105例双侧肾发育不全、严重发育不良或多囊性发育不良的胎儿进行了研究。分析了RET和GDNF编码序列、启动子中的进化保守非编码区（ecr）、3' utr和RET内含子1。对这些位点的拷贝数变异也进行了研究。结果研究发现：(1)低频率(
Background The RET/GDNF signalling pathway plays a crucial role during development of the kidneys and the enteric nervous system. In humans, RET activating mutations cause multiple endocrine neoplasia, whereas inactivating mutations are responsible for Hirschsprung disease. RET mutations have also been reported in fetuses with renal agenesis, based on analysis of a small series of samples.Objective and methods To characterise better the involvement of RET and GDNF in kidney development defects, a series of 105 fetuses with bilateral defects, including renal agenesis, severe hypodysplasia or multicystic dysplastic kidney, was studied. RET and GDNF coding sequences, evolutionary conserved non-coding regions (ECRs) in promoters, 3'UTRs, and RET intron 1 were analysed. Copy number variations at these loci were also investigated.Results The study identified: (1) a low frequency (